Reminiscences – the DpN lab story in IISc (1997-2012)
Picture 1

It is hard to believe that more than fifteen years have elapsed since I joined the Department of Biochemistry on 30th June, 1997! It seems only the other day that I arrived by train to Bangalore along with my luggage, including a crate of dry ice containing frozen mammalian cell line, plasmids and bacterial stocks. The move from the University of Cincinnati to the Department of Biochemistry, IISc, one of the oldest Departments established in 1921 (Picture #1), in this part of the world was anxious but also an opportunity to begin a new life as an independent faculty member! It was nice of Prof. R. Maheswari, the then Chairman of the Department of Biochemistry, IISc to receive me at the railway station. The frozen stocks of cells were kept in Prof. A. Karande’s liquid cryocan and I started my work by thawing the cell lines in Prof. R. Manjunath’s laboratory – the transition of work done abroad to here had begun! The first five years passed in a blink (Picture #2) and there was not much time to reflect as survival was the main priority! We did celebrate ten years of the lab by going to a resort near Bangalore (Picture #3) and to celebrate fifteen years of the lab we went trekking (Picture #4). A lot of water has flown down the river Kaveri since the lab began and, perhaps, fifteen years is an appropriate mid-career moment to reflect and put some thoughts down on paper. I will focus on the broad picture of the laboratory and life in IISc in this piece. I hope I have not forgotten any important aspects – in fact, the fear that I may forget key nuggets of information was the driving force in penning my thoughts before memories are lost with age!

Picture 2

Disclaimer: All the thoughts and opinions expressed in this article are solely that of the author and not of any Department or Institution.

 

Picture 3
Picture 4
IISc
Picture 5

The best part of IISc is its academic environment - scientific research does not flourish in isolation, and a culture of research is present here (Picture #5). There is a huge amount of freedom to pursue projects of one’s choice, an aspect that is so important for the creative process. For example, the main areas of interest of the lab right now are very different from the ones that were present at its inception. One goes after findings as they arise and following them to completion is the fun part of the journey along with its twists and turns. IISc has a large collection of talented faculty, perhaps the largest group of scientists working in diverse disciplines in India. Classes and meetings start on time – this may seem trivial but this is not how it works in several other parts of India. It has an University environment and spending time with young and bright students is invigorating and slows down the aging process!

Picture 6

One of my personal favourites is the flora and fauna present on campus. To walk across the wooded campus with a large canopy and to listen to birds roosting in the evening is a unique experience – one that I cherish and am thankful for. In fact, the temporal flowering of the trees correlates with the month here: late December and early January is filled with blooms of the purple tabebuia. By February, the yellow tabebuias are in bloom (Picture #6) and by March, the pink tabebuias are in their fine splendour. As the heat increases, the jacarandas, bougainvilleas, queen flowers etc bloom. The peak summer is the time for the red gulmohars, spathodeas, copper pods, java cassias etc to bloom. Around March 3, i.e. the IISc Founder’s Day, the nursery puts up a breathtaking display of flowering plants and some photos are on display (Picture #7). Once the rains usher in by mid-April, some of the streets are stained red due to the fallen gulmohar flowers (Picture #8). It rains in Bangalore from mid-April to November end and the hot months last for three months: mid-January to mid-April. In general, the weather is one of the plus points of Bangalore as it is exceedingly pleasant for the majority of the year.

IISc is set up as an island, i.e. one can live inside the campus, go off to work and live life without stepping too much outside: shopping can be done at the bazaars here, kids can be sent to the nearby Kendriya Vidhalaya school etc. It is useful to get some protection from the outside world: upon our arrival, we stayed inside campus so as to avoid the traffic, pollution and uncertainties of the big and noisy world outside. The existence of the Health Centre inside campus is most useful. It takes care of small niggles as well as bigger problems that do crop up. There have been at least two emergency situations when students from my laboratory have been taken to the health centre. In one case, the student had to be rushed to the nearby Ramaiah hospital and the Health centre made all the necessary arrangements. The IISc doctor concerned was with me outside the Emergency room until the student recovered.

Picture 7

Notably, the changes that occur in India often reflect in, perhaps a bit slowly, the changes at the Institute. A classic example is the one concerning hostels for women students: several years back, there were very few women students, resulting in the absence of hostels for women. This aspect is covered in a short story by Sudha Murthy during her stay on campus and on her interactions with the industrialist J. R. D. Tata (https://www.facebook.com/note.php?note_id=130004007048106&id=541419787). However with time, the number of women graduate students has increased and so have the hostels for them. It is educative to sit through the interviews for selection of students every year in June. Students arrive from different parts of India to try to secure admission here. It is quite an experience to fathom the sheer diversity of students and get a feel for their stories as they aspire and compete with each other to secure an entry into the PhD program. Renewal in IISc occurs every year with a fresh intake of students every year in August. During the second week of August, newly admitted students and faculty are treated to a snacks/tea as part of their welcome. The theme here is that change is good and the old must make way for the young as is the norm of life. In IISc, students are the key and the support network among them is great; there is a lot of sharing of resources after faculty go home at the end of the day. I suppose they miss all this fun after graduation but some good friendships last life-long! In general, students from here have done remarkably well with respect to career advancement as judged by the high quality of publications in their postdoctoral research or after being hired as faculty in national institutes and Universities in India. Some have even become Directors of prestigious institutions!

Picture 8

The tranquil environment in the campus belies the dynamic, fast paced and intense research activities and events here. The system is big enough to sustain periodic upheavals and move on. From the outside, IISc appears to be quiet but most students work feverishly and are highly competitive. Also, students learn to interact and share reagents/compounds required for their work from other laboratories. In other words, there is some amount of “redistribution of wealth” that occurs after faculty leave in the evening. This may be useful as it takes time to get reagents for experiments here. Several students observe and learn in this atmosphere and some of them go on to become faculty here and in other institutions. IISc, in other words, is a major resource for generating PhDs and a breeding ground for faculty in the future. The competition among students to do well is intense and allows for selection of some of the best. With time, each laboratory develops a phenotype and students work at different paces. There is no set way of doing things here which leads to a “live and let live” philosophy; consequently, all phenotypes coexist. This is certainly good as the phenotypes are distinct and the system allows for the establishment of independent phenotypes. Importantly, one does not need to follow the herd, can remain distinct and establish a unique phenotype.

One trait that works here is INDVIDUALISM - everything here is individual driven! While individualism works, it may also sometimes be associated with selfishness, which is a source of worry. There is no point in complaining about the system as exceptions abound and individuals here are either able to manage or not. Most do survive and some do very well, it is like a bell shaped curve. In IISc, passion triumphs and one has to keep on pushing away without getting disheartened until the system finally gives in. The other side of the coin is also prevalent, i.e. if a person expects the system to provide too much, one is liable to get disheartened. Therefore, one must try and make the efforts to do as much as possible. In my observation, at least in the Biological Sciences Division, another trait that is important is the ability to manage people. Some people are just better managers and it makes a big difference as most of the work here is done by students. Most new faculty members are untrained in this and other aspects, e.g. keeping accounts of grant funds etc. It may be useful for them to become aware and learn these aspects which will help them in their job as faculty. It is certainly possible to do very good work, in some cases, exceptional work gets published in top notch journals. Sathees Raghavan’s paper in CELL this month from IISc is an excellent example! This was certainly exciting and he certainly deserves more power to be able to pull it off! Importantly, it reinforces all the points in this paragraph.

During this journey, the support from my family, including Vrinda - my better half, Jaidev and Mira - our kids, parents, in laws, extended family members and friends have been tremendous for which I am grateful. One of the problems with nuclear families is the issue with support once a member falls ill. Under these circumstances, life becomes complicated as we do not live in isolation. Therefore, let me restate that the support, health and well being of all family members and friends in sustaining work done by faculty/scientists is underappreciated and needs to be recognized.

The laboratory has done reasonably well in these fifteen years: thirty publications, five book chapters, nine PhDs, one US patent, several general articles, book reviews etc. Of course, we should have done better! However, whatever has been achieved has been primarily due to the efforts of students. Therefore, let me expand a bit on each of the students of the laboratory who have spent time and contributed to the growth of the laboratory.

First generation research students

Dilip Chandu:
The first graduate student is always special and I could not have asked for a better one than Dilip who joined in 1997. It was a little hard for Dilip as there was no laboratory in the beginning, just an empty and dirty room that was in urgent need for renovation. It took some time for the laboratory to be refurbished but Dilip got going with his work and never complained (at least to me). At that time, his goal was to biochemically characterize the eubacterial 20S proteasome (high molecular weight) in Mycobateria. However, as a control E. coli that lacks the classical 20S proteasome was used.  He detected biochemical activity in E. coli extracts in the low molecular weight range. Dilip identified Peptidase N (PepN) to be responsible for cleavage of a peptidase substrate, Suc-LLVY-AMC, which is commonly used to assay for 20S proteasome catalytic activity. He used a combination of genetics and proteomic analysis to identify this enzyme. Subsequently, he showed that PepN is responsible for majority of the detectable aminopeptidase activities in E. coli. Despite having good bench and analytical skills, Dilip got the BIG break only after four years.  After he had his break, I remember celebrating with him by going out for tea at the kiosk nearby. I told him that such breaks are rare and one must celebrate such occasions. When we submitted his work to J. Biological Chemistry, there was a lot of back and forth between us and the referees. At the last stage we were getting anxious due to the long delay – finally, I enquired about the manuscript to the Associate editor. After hearing from her, I informed Dilip by email that the delay in the formal acceptance of his paper was due to a storm in the Washington DC area at that time!

I remember that when Dilip showed his data on the observation that PepN was the major aminopeptidase, several people enquired on the physiological relevance of this observation as both WT and ΔpepN grow well in Luria broth. Parag, my buddy who was an expert on stress responses (see below), suggested that some clues may be found in the literature or microarray data bases by studying the modulation of pepN expression during different conditions. Indeed, Anujith found a paper showing up-regulation in pepN expression during sodium salicylate stress, a model of xenobiotic stress for E. coli. Dilip quickly followed up on this after getting some sodium salicylate from another laboratory and showed that pepN reduced the ability to resist some stress conditions. This finding was published in Microbiology in 2003.

Dilip was very disciplined and the first one to be in the laboratory in the morning. He would read up literature and come up with ideas on his own. The PepN story has been one of the mainstays in the lab and, over the years, we have contributed a lot of knowledge with respect to its biochemistry and functional roles. In other words, we can claim to have made an honest contribution in this particular area. While working on Dilip’s thesis introduction, we decided to write two reviews. In the first, we used a combination of bioinformatics and review of literature on the microbial proteases, Lon and Clp. This combination worked and resulted in a publication in Research in Microbiology in 2004.  The other was a review article on ubiquitination – it was in the news at that time as the Nobel Prize was awarded for this area in 2004. At the time of writing this review, we didn’t realize that this review in J Bioscience would be such a big hit after its publication in 2006. As of this month, it has been cited more than 180 times. There are very few articles published by Indian authors in Indian journals that do so well. It is certainly a case of “small” story that becomes BIG – we must have done something right!

Apart from his research studies, Dilip was also busy with other activities: he met Abha, who was doing her PhD is the neighbouring MCBL department and would eventually be his wife. Abha has incredible energy and it was nice of her to find the time and visit our home several years later during a visit to Bangalore. Dilip submitted his thesis in 2003 and left for a postdoctoral stint in Washington University, St. Louis, MO, USA. Abha and he must have like the city as both are working in Monsanto, St. Louis right now. Several years later, Dilip informed me that his friend, Deepak Saini, from Washington University will be joining the MRDG Department as faculty in 2010. Over time, we got to know Deepak and his family who have become a part of the support network that is so essential.

S. Jyothi Prasanna:
If there is one word to describe Jyothi it would be “gutsy” – she is a true survivor who could beat the odds. After the merit list was announced in June 1998, Jyothi came to our quarters and announced that she would, most likely, be allotted to my lab. She turned out to be highly emotional and declared that she would work as hard as possible but would like to complete her PhD in three and a half years. Soon after her pre-viva, Jyothi got married which gave her stability and a structure.  She realized that she had to complete all her work in between 9 am to 6 pm and couldn’t afford to waste time. She started studies on the role of the immunoregulatory cytokine, Interferong (IFNg) on the hepatoma cell line H6. In the process, she noticed differences in the cell surface expression of two MHC class I alleles. Subsequently, she studied the different requirements of assembly factors for surface expression for these two mouse MHC class I alleles, Dd and Kk. In fact, her paper in the Molecular Immunology with a diversity of experiments, e.g. transfections, FACS, 35S-labelling and immunoprecipitations etc, is truly a “mother of all papers” to be published from our laboratory. Notably, all the experiments were performed by her.

The other interesting observation that Jyothi noticed was the growth suppressive effect of IFNg on H6 cells. However, the mechanisms were not known. At that time, Sam, another graduate student, was working on the roles of reactive oxygen species (ROS) on T cell activation. This led to the investigation of the roles of ROS and reactive nitrogen intermediates (RNI) in her system. It worked like a charm and the work clearly demonstrated the roles of ROS and RNI during IFNg mediated growth suppression. This part of the work was subsequently pursued by her junior, Bani, and published in International Immunology. In addition, Jyothi validated results of a microarray analysis and identified several genes modulated by IFNg. After she completed her experimental work, Jyothi took leave to deliver a baby and submitted her thesis in 2005. The best part was the involvement of entire lab in helping her to put the thesis together to ensure that mistakes were minimal. We have been following this model in the lab with others too as it reduces mistakes and is a learning process for the younger members of the laboratory.

Post PhD, Jyothi works on stem cells and manages commuting, teaching and running an active lab. It has not been an easy ride for her but true to her gritty nature she has stuck it out and is, currently, an Associate Professor at the Manipal Institute of Regenerative Medicine, Manipal University.

Prasanta Maiti:
Prasanta was my first postdoctoral fellow and joined the lab under unusual circumstances. Apurva Sarin, with whom he had joined in the Department, decided to move to another Institute (NCBS) and he had to find a laboratory. He was interested in Immunology work but I knew that setting up facilities here would take time as the laboratory was still trying to find its feet during the early years. Initially, we started thawing the hybridomas in Prof. Manjunath’s laboratory. I recall that we were not able to thaw live cells from the vials containing hybridomas secreting anti-CTLA4. Finally, the last vial was thawed from which live cells grew out! This tuned out to be serendipitous as the initial studies on T cell activation were with this antibody. Prasanta is a quiet worker and standardized a method to generate ascites for several hybridomas, including the extensively used anti-CTLA4 and mCTLA4. Finally, he set up the initial T cell activation assays with these antibodies. Upon seeing some of the initial results, I realized that this observation would need some time to be followed up further and a graduate student would need to be involved. Ultimately, Sam worked on this initial observation and developed it for his thesis study. Over time, I have realized that this “synergy” model between two people in the laboratory works well: usually a graduate student and a junior research fellow (JRF) or a postdoctoral fellow and JRF or older graduate student with a younger graduate student. Prasanta left for his postdoctoral studies in Israel followed by another stint in the US. He relocated back to India and works in a company in Bhubaneshwar. It is indeed nice of him to take special efforts to meet me whenever I visit that city.

Sambuddho Mukherjee:
On January 1999, Sam, an Integrated PhD student, informed me that he would like to do a rotation in my laboratory. Sam picked up the cellular immunology work very quickly; he was as comfortable as a fish in water. He was also very adept with computers and played round with different FACS based softwares. He was helpful in setting up the Departmental FACS computer, trouble shooting for the FACS facility and helped other faculty with their problems with computers etc. For his doctoral studies, he standardized the procedure for isolation of CD4+ T cells and established the “strength of signal” (SOS) activation system in the laboratory. Like life, his studies underscored the roles of optimal activation of T cells: a low SOS is insufficient whereas a high ROS leads to over-activation and death of T cells. Importantly, he demonstrated the differential roles of CTLA4-CD80/CD86 interactions in modulating T cell activation based on SOS. It was difficult to interpret the initial results with the reagents and different activation conditions. I remember walking around the library one evening when it all came together in a flash – the mind does work in mysterious ways! Sam’s first paper in J. Leukocyte Biology in 2002 was the first real publication for the laboratory which was a cause for much celebration.

A part of Sam’s work involved studies with a molecule known as fetuin which binds to TGF-beta. This was obtained from Prof. P. Kondaiah who was extremely generous and I do appreciate this gesture. While Sam was performing his T cell studies, he noticed some functional roles for ROS during T cell activation. In this context, some interactions with Prof. T. Ramasarma proved to be extremely useful. An off shoot was the screening of small molecules that affected T cell activation which led to the identification of some plant auxins in simulating T cell activation. Sam submitted his thesis and left the laboratory in late 2004 for his postdoctoral studies. He has remained in the field of Immunology, has grown and done well during his postdoctoral studies. I am sure that he will do well in his career ahead.

Veerupaxagouda Patil:
Veeru joined in 1999 and worked on several projects. He was not terribly excited with the in vitro work going on in the laboratory – some criticisms are right on the target! It was a struggle for Veeru but he decided to set up an in vivo model of infection using S. typhimurium. I remember that he called me in December 2004 to declare that he had found a difference between the wild type S. typhimurium and the mutant lacking pepN. Veeru submitted his thesis in late 2006 and his story was published in FEMS Microbiology and Immunology in 2007. I remember that during lab get togethers, Veeru’s choice of food was very different from others as he liked to experiment with foods with strange sounding names. The best part about Veeru was that he did not give up despite difficulties and completed his thesis. His contribution to the lab is a lot as we have been continuing with the S. typhimurium infection system since then.

Second generation of students

Anujith Kumar:
Anujith was the second student to follow up on the PepN work. He joined in 2001 and turned out to be highly skilled with tons of desire to do well; in addition, he has a congenial personality. During the initial stages, he generated the pepN lacking E. coli strain that was useful to convince referees that PepN was indeed responsible for both amino- and endo-proteolytic activities. It is only later that we realized that several knockout strains could be obtained and confirmed from E. coli stock centers. Anujith made the pepN lacking strain in S. typhimurium and this was important: it is not easy to procure gene knock out strains in S. typhimurium as it is an intracellular pathogen and it is best to make them in the laboratory. Anujith used the S. typhimurium pepN lacking strain to show the role of PepN during nutritional downshift and high temperature (NDHT) stress. At first, he got a small difference between the WT and ΔpepN with nutritional downshift stress alone. During discussions over tea, Parag suggested that sometimes dual stress work better and this led to discovery of the role of PepN during nutritional downshift and high temperature (NDHT) stress which was published in BBRC in 2007. I suspect that the real physiological role of PepN occurs during multiple stress conditions, which may be more relevant. The response of organisms to single stress is a laboratory oriented way to study environmental stress conditions. Organisms, including us, face multiple stress factors and, perhaps, it is more physiological to study our ability to resist and overcome these.

The bulk of Anujith’s work centered on the generation and characterization of PepN mutants e.g. C-terminal deletions and site-specific mutants. We collaborated with Prof. N. Srinivasan, MBU to develop structural insights using his prowess at modelling. While it took us years to generate and characterize the mutants, Srini would complete the modelling work in few hours – amazing! In addition, Anujith performed a screen to identify the roles of ATP-dependent proteases in resisting different stress conditions. This work is currently being performed by Chetana, a graduate student, as part of her PhD studies. Anujith published several papers but the best part of him was his helpful nature: we worked closely to get a lot of writing done for another student’s thesis. This was necessary as the student could not work for sometime and help was required and I do appreciate his understanding of the situation at that time. Anujith submitted in 2007 and went abroad for a postdoctoral fellowship on stem cells. He has returned back to India and is, currently, an Assistant Professor at the Manipal Institute of Regenerative Medicine, Manipal University. True to his nature, he is anxious about the future, works hard and is constantly thinking of ways to increase his funding, better his publications etc. I have no doubt that his drive will serve him well in the future.

Pankaj Tahiliani:
Pankaj joined the laboratory as a postdoctoral fellow after completing his PhD from Devi Ahilya University, Indore. His positive temperament and helpful nature are outstanding features and he started working and completed a project on Leptospira which no other student was interested. In addition, he contributed some excellent figures in the ubiquitination review published in J. Bioscience. Another noticeable aspect was that he was clear on his future plans, unlike most students who are fuzzy and tend to go with the crowd. He realized that academic life was not his cup of tea and joined industry. His “go getter” attitude has worked well for him and I am very happy that he has done very well in his career. 

Banishree Saha:
Bani joined the lab in 2002 and her ability in “taking diverse people along” became apparent. She followed up on Jyothi’s observations with the H6 model system and decided to choose the Ras activation for further study. This turned out to be a wise choice as the role of Ras activation by IFNg was not well studied. To give some physiological relevance to the IFNg story, she decided to standardize the acetaminophen (APAP) drug-induced model of hepatotoxicity. She chose this system as H6 is a hepatoma cell line and IFNg lacking mice are insensitive to APAP-induced hepatotoxicity. She spent considerable time standardizing this system and showed liver damage was initiated after oral dosing of Acetaminophen. Liver cells are highly sensitive to oxidative stress and this damage could be prevented by injecting L-methionine, which prevented oxidative stress. Using this system, Bani demonstrated that a Ras inhibitor, Manumycin, could block APAP-induced liver damage. At that time, there were several studies that showed the role of JNK in enhancing liver damage but Bani showed that Ras was upstream of JNK activation.

There is a story about the publication of this work that I would like to share. I was a bit apprehensive of the work being accepted in a high impact factor journal as it was dependent solely on chemical inhibitors. However, Bani made a wise choice by selecting the journal Hepatology which, incidentally, has a double digit impact factor. There was the usual back and forth between referees and us. Also, we got some help from Vrinda and her friends in Astra Zeneca with respect to setting up some assays that were required to satisfy the referees. As the final revision was being done, I realized that the manuscript needed to be cut by ~500 words which was not easy. I had hoped to get it all done soon before the deadline so that I could watch the memorial service of Michael Jackson in July 2009. His dance moves in the album “Thriller” had first caught my attention while I was studying for my Masters degree at the M. S. University, Baroda. Nevertheless, I saw the service along with my son, Jaidev, and the song “Smile” sung by Jermain Jackson at that event was appropriate and extremely touching. After watching the event late at night, I came back to the lab, edited and uploaded the document by early morning; the manuscript was accepted soon after. I mentioned to Parag that the Editorial board member must have also been influenced by the concert and accepted the manuscript quickly. I shared the good news of the acceptance of the paper with lab mates with a celebration at “Mint Masala” – our first of many outings at this restaurant. In the evening, I took family members, Parag and his parents who were visiting for dinner at Mainland China. We were all happy at this “hit” from the lab.

Bani trained her junior, Bhagawat, who performed bioinformatic studies of IFNg-regulated genes with respect to the presence of binding sites of the key transcription factors, Stat1, Irf1, AP1 and NF-kB. Once again, the combination of bioinformatics and linking it with literature, this time on the roles of IFNg, led to a publication in Cytokine. In addition, Bhagawat followed on the APAP-induced liver toxicity model and collaborated with Rekha Gautam in S. Umapathy’s laboratory in the Inorganic and Physical Chemistry (IPC) Department in IISc. This study led to the identification of tissue and serum biomarkers for APAP-induced hepatotoxicity and was published in PLoS One this year. The main focus of Bhagawat’s work is on peritoneal macrophages and their responses to IFNg that are regulated by Nitric oxide synthase 2 (Nos2) which is the main enzyme that generates NO in macrophages. We decided to switch from the cell line H6 system to the primary macrophages model as it is more physiologically relevant, one that can be dissected using knockout mice. He has shown that some chemokines are regulated in a Nos2 regulated manner in his J. Infectious Diseases paper that was accepted a few days back. Some of his imaging studies on these cells are interesting and will, hopefully, be communicated soon. Overall, I think the move from a tumor cell line (e.g. H6) to the macrophage model which has implication in immune and inflammatory responses was a good choice and should stand us in good stead in the future.

After the submission of her thesis in 2009, Bani moved to Delhi to work in a well known liver lab – guess the “liver bug” must have bitten her! After some time, she felt that it would be better for her growth to gain some postdoctoral training from abroad. She is currently at the University of Massachusetts Medical School, Amherst, USA and I hope she will start her own laboratory and independent career soon. 

Asma Ahmed:
I was surprised but happy with Asma’s decision to choose our laboratory in 2002. In the interviews she had said that “molecular biology” was her first preference; however, when it came to the choice of a laboratory she picked ours. Later, she explained that she was more confident in questions related to molecular biology but was interested in Immunology as a research topic. Asma was a good student and a “solid” worker. Periodically, I would be pleasantly surprised at her overall general knowledge, the history of India etc. She suffered from respiratory allergies but did not allow her work to suffer. She picked up the T cell work quickly, learnt from Sam and helped to complete several of the T cell projects. She published two first author papers in Immunology and International Immunopharmacology. In addition, Asma is a good writer and helped the laboratory with writing some grants. Asma’s work on the roles of calcium and reactive oxygen species in modulating T cell activation by CTLA4 blockade constituted a huge amount of work. The major phenotype of CTLA4 as a negative regulator of T celll activation was shown in studies using mice lacking Ctla4. There have been some studies showing the enhancing of effects of CTLA4; however, we have not been following up on this as our studies were all in vitro. Instead, we have been focussing on some aspects of the SOS. Also, the T cell activation studies helped us to investigate anti-tumor T cell responses and diversify into thymocyte biology in the later years.

I remember Asma for some things that she said and these have left an impression on me. The first time I met Asma I asked her as to why she wanted to be in science. She replied that she wanted to make a contribution. By the way she spoke these words, it was obvious that she meant it and it was coming from somewhere deep down. Years later after she completed and visited the laboratory on a trip to Bangalore with her son, Abizer, she confessed that she missed IISc a whole lot: one takes the campus and its natural beauty for granted; it does have an effect on you and one realizes it only after one has left the place. Perhaps, the best compliment to Asma came from one student who belonged to another laboratory. This student was Asma’s junior by three years but he told me that he would like to do more quantitative Immunology in the future like Asma – ‘impacts’ are made in different ways in life! Asma is doing her postdoctoral research in Hyderabad and should continue to be involved in science and teaching.

Current students and status

Out of the third generation of students, both Manoj and Mukta have submitted their thesis within five years. Manoj joined in September 2006 during a testing phase for the laboratory. The student who had joined in August 2006 left suddenly and I needed another student to learn and continue the PepN work after Anujith. Manoj rose to the challenge, worked hard, networked better and completed several projects, notably the C-terminal PepN paper. The use of E. coli lacking pepN to express and screen for novel protease/peptides for their substrate cleavage profile was an idea that was around in the lab for a long time. However, it was Manoj who completed the work which was published in BBRC in 2010. Some of Prof. Manjuanth’s suggestions have worked very well for Manoj and resulted in publications. He has grown in these years and has been lucky for the laboratory, which is good! I remember that one of his papers got rejected; it turned out to be an administrative mistake and it, subsequently, got accepted in the same journal. Manoj is a gentle big guy, good with people – I hope he uses these skills to become an entrepreneur in Biotechnology and will employ and help people in the future.

Mukta worked on the mechanisms involved in thymic atrophy during S. typhimurium infection and will have her open defence soon. The observation that CD4+CD8+ thymocytes undergo death during infection with S. typhimiurium was made by Veeru; however the mechanisms were not known. Mukta standardized the oral infection model and has done a remarkable job in uncovering the roles of glucocorticoids, IFNg, signalling proteins etc. In addition, she set up a mono-microbial model of sepsis in the laboratory. She is extremely skilled, works hard, possess tremendous amounts of energy – in fact, I was a bit worried when she worked liked a ‘woman possessed’ while completing the experiments suggested by referees for Asma’s auxin paper. She has collaborated with several people on different projects and this has been a useful experience for her. She has a first author publication in Immunology and more are likely to follow. She has been remarkably positive and I am sure that she will do well as an independent investigator after undergoing post-doctoral training.

Srabanti joined as a postdoctoral fellow in 2007 after completing her PhD from the Indian Institute of Chemical Biology (IICB), Kolkata. Her PhD Supervisor, Dr. Santu Bandyopadhyay, is one of finest and most helpful people that I have met in these years. Srabanti has the longest commute in the laboratory but she worked very hard and standardized the Mycobacterium indicus pranii (MIP) story along with Mani, a JRF. The Sp2/0 tumor model was initially set up by Bani and Srabanti and Mani showed that intradermal injection of autoclaved MIP reduced tumors. Now, the role of bacteria in inducing immune responses is known since William Coley’s pioneering work in this field since the late 19th century, i.e. around 1890s. However, Srabanti showed that the ability of heat killed MIP to reduce tumor growth is due to the induction of IFNg and anti-tumor T cells. It was certainly useful to have the T cell expertise in the laboratory as this work involved studying anti-tumor T cell responses. In addition, studies were performed in different strains of mice, including two mutant mice strains – one of which was procured from Mumbai. Finally, this long and detailed study was accepted in the International Journal of Cancer in 2011. In addition, a US patent showing the synergistic efficacy of MIP and Cyclophosphamide in reducing tumor growth has been accepted. Srabanti has performed additional studies on the roles of free radicals in mediating some effects of IFNg and studied other effects of MIP. Hopefully, these studies will be published soon so that she gets full credit for all her efforts. Her research experiences in the areas of free radicals, cancer, cell biology and imaging have been useful to the laboratory.

Apart from PhD students, there were four Integrated PhD students, Srividya, Shruti, Subhash and Tanushree, who have secured their Masters degrees from studies in the lab. The fact that all these students have contributed to publications from the laboratory is certainly good news. Srividya and Shruti had joined during the early years of the laboratory and brought in a lot of youthful energy. They developed a bioassay for Interferon-gamma using the production of nitrite as a readout by primary peritoneal cells which was published by the J. Immunological Methods in 2003. Years later, Bhagawat would make interesting observations using this system for his PhD work – sometimes, I think, we work in circles! Both Srividya and Shruti went abroad for their PhDs and have published in well known journals. The current batch of postdoctoral fellows (Srabanti, Manoj and Mukta) and PhD students (Bhagawat, Chetana, Shamik, Supriya, Semanti and Shikha – the last four have their names beginning with the alphabet S, i.e. S4 – (is this evidence for directed selection?) are motivated and I am sure they will do well.

As seen above, some of my PhD students after their postdoctoral training are working in academic institutions or companies. Career options, like life, are competitive and complicated in today’s world. It is understandable that each student finds her/his individual road (sometimes rocky) to happiness. For me, it is satisfying that some of graduate students from the laboratory have or are starting their careers as independent researchers and some have even published on their own! I do keep in touch with all students, including JRFs and summer students, by sending then articles that I like by email. Sometime, I hear back from a few of them in case they “connect” with the article. It is nice to hear from them at periodic intervals.

Research fellows

Apart from the PhD students and postdoctoral fellows, the lab has benefited from several research fellows, many of whom are listed as coauthors in our publications. Initially, all the work including ordering chemicals/reagents was performed by graduate students and it is only later that we could afford some research fellows. In general, the research fellows who have done well are the ones who worked “in synergy” with a graduate student. Sanjana joined in 2007 and was instrumental in quickly learning the S. typhimurium infection model. Together with Anujith, she completed the experiments required for Veeru’s paper. The interaction of Suri with Anujith was productive and led to several papers. A special mention must be made of Mani who was in the lab for a long time. Together with Srabanti, he synergized well to complete the tumor studies; his name is on the US patent too. Suni Chacko was the “lab mom” for some time and her gentle nature was helpful in ensuring that the lab functioned well. The current two research fellows in the laboratory, Mrinmoy Das and Emmanuel, are outstanding and have already several publications to their credit. They work hard, are more skilled, and are more disciplined than some graduate students. I wish there were mechanisms by which deserving research fellows could be awarded more credit, may be even degrees, for their scientific contributions that help the laboratory.

Lab helpers

Soon after joining IISc, I was surprised when Nagaraja, a laboratory helper, came over to meet me. He explained that Prof. Poddar was retiring and he requested a transfer to my lab. At that time, I did not have a functioning lab but agreed to his proposition. Lab helpers are associated with a laboratory and their salary comes from the Institute as they are permanent employees. He described himself as a “meat eating Gowda” and his perspective of the world is very different from the middle class thinking and attitudes of most faculty and students. It was enjoyable having discussions with Nagaraja and he was very helpful during the initial phase of setting up and running the laboratory. The permanent job in IISc ensured that he could build his own house and educate his two kids. His family owns large pieces of land in the outskirts of Bangalore in which rice is grown. I remember visiting his house for the “grihapravesh (house warming)” along with students and appreciating the social transformation that is occurring in India. As Nagaraja grew older, he started taking a lot of leave and the huge pile of unwashed glassware annoyed the students – and me! Shortly after the move to the new building, he transferred to another laboratory. Right now, we have a part time person as a lab helper and she comes every afternoon, washes glassware and keeps the laboratory clean.

Summer students

A fleeting population in the laboratory have been summer students. I think it is a good opportunity for students from different parts of India to get an exposure to research in IISc – it does make a difference at their young and impressionable age! In addition, they come in contact with senior students and it helps them to learn and network. Overall, it is interesting to meet such young students and there are some who have made an impression.

Abhishek Tomar travelled all the way from Indore to express a desire to work in IISc as a summer student in 2006. He came up with an expansion of the acronym DpN which I appreciated very much:
D – Determination
P – Perseverance
N – Non stop (working, I suppose).
Abhishek did his PhD from the University of Groningen in the Netherlands.

Anand Patwardhan, a student from Pune, did his MSc from Shantiniketan. I liked the geographical transition that he made from the West to the East to pursue his studies and was glad that he was selected for PhD by NCBS, Bangalore. Shweta, another student who spent the summer of 2008 in the lab made beautiful illustrations which are a part of our review articles in Resonance. She is, currently, doing her PhD in IISc.

Mrinmoy came as a summer student in 2010 and worked with Manoj. The two of them hit it off and Mrinmoy identified mutations in PepN that altered substrate specificity of the enzyme. Both Manoj and Mrinmoy (currently a JRF in the lab) are trying to complete this story. Another summer student, Ahanjit, a KVPY fellow, also made an impression. I think he will do well working in the area of bio-metals as he has found a calling.

Unfortunately, I cannot mention all the summer students due to lack of space. In their own ways, all the summer students have contributed to the liveliness in the laboratory. It has been a BIG BONUS if they have uncovered an interesting observation. Several of them have gone ahead to pursue a doctoral degree which is a good sign. I do think that it is a good opportunity for summer students to get a taste of IISc as it is likely to make a positive impact during the early years of their careers. I recall a pertinent observation from my friend, Evan Hermel, while we were doing postdoctoral research at the University of Cincinnati: in academia, one gets to meet to new people for a short while, e.g. summer students, at scientific conferences, etc and these interactions need to be treasured!

Parag, my buddy

When I arrived in Bangalore, the only friend that I knew was Rana, more famous as Anindya Sinha, who works in the National Institute of Advanced Research (NIAS)! Rana is a special person and I quickly realized that during our first meeting when I was in TIFR as a summer student with Dr. L. C. Padhy in 1986. I am glad that our families are in touch and our kids go to the same school. Over the years, I have been lucky to have established rapport with several people in IISc: R. Manjunath, Saumitra Das, Utpal Nath, D. N. Rao, Umesh Varshney, V. Nagaraja, A. G. Menon, Vidyanand Nanjundaih (Vidya), S. Mahadevan (Mahi), Deepak Saini, to name a few, all of whom have been very helpful at work and at the family level. Among my friends, it is sad that the person with whom I shared most of my experiences during the past years is no longer with us.

Picture 9

Shortly after my move to IISc, Parag and I became friends - he became my buddy (Picture #9)! We shared some common strings: both of us are from Bombay (now Mumbai), did MSc from the Department of Microbiology, M. S. University (MSU), Baroda and his parents live in Bandra, Mumbai, the place where I grew up. He was my grand senior in MSU but I did not know him then. We were also very different as he was very sensitive, emotional and prone to get hurt easily – although he would not show it! Perhaps, he was a dreamer whereas I am a realist. He would often chide me on my natural impulse to see issues as “straight” whereas he saw them as “fuzzy”. As we disagreed on most topics and situations, it made way for long conversations over tea. We would meet at least once or twice a day: once for a walk to the faculty club for lunch and again, usually, late evening. In the later years, Utpal Nath also joined us for lunch at the faculty club, which was a place to unwind, find out about events occurring in IISc and elsewhere and gossip. There were others who were a part of the lunch session: Nagaraj, Umesh, D. N. Rao (early years) and Vidya, Renee, Mahi (later years) etc. For the past few years, Parag was fond and enjoyed the company of a faculty member fresh from Yale, Pravin “half pants” Karanth. Upon looking back, those were carefree days indeed!

I enjoyed the time with Parag - on some Sundays, I would go to his apartment and we would spend time discussing issues over tea. I think he enjoyed these unplanned meetings more! He relished the company of kids and was able to relate to them very well. He was extremely encouraging about our laboratory studies and attended the research presentations of most of my PhD students. I would joke that he was our only true supporter! His friendship reinforced the importance of support that is important, especially when the chips are down, which is common in research. Parag’s laboratory started work on Candida and made some interesting observations with a mutant. He had a strong desire to make the story BIG and collaborated with several groups: NMR studies were performed by a company whereas immune function related studies were performed by our laboratory. It took some time but the manuscript was finally accepted by PLoS Pathogens in 2011. He was delighted that all his efforts resulted in a good publication and we went for lunch party at a five start restaurant in December 2011 along with Utpal Nath and his friend from JNU, New Delhi.  

During my initial years, I recall that Parag would take his students for tea; however, with time, he would go for tea with me or other colleagues - one does differentiate with age! His loss on Janaury 20, 2012 was traumatic! To be present and to share this grief with his aged parents and other family members made me close to them. Among the several emails that I received after his passing away, the most touching was from his PhD mentor who wrote, “Wish I was there during the difficult times to help him in a different sort of way.” This sentence sheds some insights on the close relationship between a mentor and a student. This close bonding exists in some faculty-student relationships and represents an important aspect of academic life. For more details on Parag’s contributions and other details on his life, please see http://eprints.iisc.ernet.in/44391/1/cur_sci_102-6_2012.pdf. In addition, a write up on the effect that he had on a student who was doing a short project is touching, http://www.gyancentral.com/articles/graduate/science/a-tribute-to-professor-parag-sadhale. A sense of closure was finally achieved six months after his death during a Hindustani classical music recital organized on his birthday which fell on 16 June 2012. It is ironical that while he was alive, I had never celebrated his birthday. His loss led to changes in my routine. I have avoided going to the faculty club since January 20, 2012 and vent sessions are now, usually, with Utpal Nath. I do remember Parag often and hope that he is at peace where ever he is!

Parag’s loss led to my “derepression” in several ways and writing is one of them! It has made me think of, and to get involved in, ways to bring younger and vulnerable faculty members together and give them a better sense of belonging! After all, one lives for others and it is important to try to make a difference! One such forum that was initiated in September 2012 is the Division of Biological Sciences lectures series and the Divisional Chairman, Prof. D. N. Rao, deserves all the credit for taking it off the ground. It is a good opportunity for us to talk about our work in front of our peers and students. Perhaps, this simple recognition gives us a better sense of accomplishments. There should be more such avenues created for younger faculty from other Institutions to meet, present their on-going work, discuss issues and in the process develop a support network. In fact, it is time that this idea is implemented at a time when faculty hiring in Biology is high in the newly constructed research and teaching institutions in India, e.g. IISERs, Central Universities etc! Perhaps, Departments and Institutions need to do a bit more with respect to “nurturing” young faculty!

Moving
Picture 10

Strange as it may seem, the move to the new Biological Sciences Building (BSB) in November end 2011 (Picture #10) was followed by Parag’s departure on 20 January 2012 – it seemed that a new phase had started! Faculty members in the Department got to pick their labs based on the architects drawings and I was happy with the choice as it has lot of windows and light – both these aspects are important for me. I am glad that I read and understood the architect’s drawings quickly and homed in on the choice of the lab.

Picture 11

Any “move” involves physical as well as psychological changes – it is easy to get comfortable with one place and not everyone has been happy with the move; however, the move was good for our laboratory. At that time (July-Nov 2011), the lab environment was not good and I felt that a change in location, would do us some good. We were among the first few laboratories to move in the Department and had started planning earlier by getting rid of lot of junk. Also, I got a huge burma teak wood cupboard (one of my inheritances from the old lab – guess it was retained there as it was too big to move) renovated so that it could fit in the new lab. The lab members put in a lot of effort but the “star” was my Maruti 800 car which transported a lot of materials (Picture #11). The downtime due to the move was short and we got work going in about 2-3 weeks, including cell culture work with Bhagawat, Mukta, Manoj, Chetana, Emmanuel and Mrinmoy leading the efforts along with others. Compared to our laboratory in the older building (1100 square feet), we gained more space (1800 square feet) in the new and swanky laboratory in BSB. Hopefully, this increase in laboratory space will allow us to recruit more students and increase our productivity. The laboratory is new and swanky and I am more in touch with the “lab chatter” as my office is located within the lab. Of course, it works both ways and students also know what I am doing in my “open” office! My nephew, who has seen both my laboratories, felt that my old lab was a “real” lab whereas the current one resembles a “corporate” lab! My huge pile of references, some from my PhD and postdoctoral days, are put away in boxes need to be reorganized. I hope to organize this some time soon – may be before the next write up in another ten years!

Laboratory function

My general philosophy is that a laboratory should allow for existence of multiple phenotypes. The laboratory, like a family, should take care of the individual needs of the members. As each individual is distinct, there should be enough space for each member to do their best. However, it is also the responsibility of each student to make use of the existing resources and apply themselves to the project. Also, students need to handle some pressure that is bound to exist in scientific research – as they say, no pain, no gain! Consequently, each student needs to figure out how to manage the work load and relax. This aspect is particularly important for the first year graduate students as they make the “book to bench” transition.

One aspect that I am happy about is that lab projects have arisen from original observation in situ, i.e. these were generated by students in the laboratory and followed up. In general, students are given some small projects to begin their studies. The hope is that during the process of investigations, the student will make an important observation which can be followed up for a PhD thesis. I learned during my PhD that it is important to work on multiple projects initially and, subsequently, focus on a few. This lesson is understood by ‘most hardworking and committed’ students and it is important to build up on observations, reproduce them and work on the mechanisms for a thesis. They need to put in the time working and learning the skills required to become a good researcher! Students need to put in an extra bit of work to make a thesis - after all, a doctorate degree needs to be earned! It is important for students to work on projects and publish their findings before leaving the laboratory. This is an important lesson to learn and one of the main challenges has been to get a junior student to complete and publish the story started by a senior student. For this, students need to ensure that they don’t allow “distractions” to be their main focus here – after all, their main reason for being in IISc is to study, perform research and also have fun in the process. In general, whatever a student needs to learn is done within four years and it is better to complete the thesis work, ensure their publications and move on. Some students become comfortable with the atmosphere here and stay on for longer periods, without getting much done and this should not be encouraged.

In some instances, the hard work of students does not directly correlate with their publication record. Although it may be a little difficult for students to appreciate at a young age, the fact is that scientific research, like life, is not always fair! Under these conditions, better understanding is required and it is important to remain positive and try alternate strategies or projects. Students ought to remember that this is a learning phase and they will need to learn and showcase their skills in their careers ahead. As an external examiner, I often find that some thesis with several prominent publications where the work result from team work, often involving many members. In some cases, the individual’s thesis preparation is also somewhat sloppy. On the other hand, there are some thesis in which the individual student’s care and efforts in preparing the thesis is obvious. Graduate education is a learning phase and it is important to focus on doing a good job with respect to thesis work.
 
Overall, I think the laboratory has worked for most students. I like students who are mature, work hard and are unselfish. Discipline needs to be emphasized and I find that students who work regular hours tend to get more done in the long run. As long as students are reasonably smart, motivated and work in a disciplined manner, luck follows – sooner or later! A good scientific finding gives a student a boost which is likely to sustain their interest. Importantly, this ensures that “small issues” that occur routinely in laboratories do not snowball into “bigger issues” that diminish the working environment! Over the years, we have worked out a system for the laboratory to function, however chaotic it may appear. I try to meet each student during a designated day during the week and having discussions with students over tea is more useful and relaxing as they tend to open up more. Lab meetings are held on Saturday morning so that there is no clash with classes or FACS / Confocal bookings etc. Each student presents the work done over the week and this ensures some form of regular monitoring. Students can work their hours but the quantum of work or lack of it shows up at these laboratory meetings. In addition, we have a laboratory journal club in which a student presents a paper that is relevant to her/his work. Journal club presentations are important to keep up with the literature and to come up with newer ideas. Going over data quickly as shown in power point presentations can be a challenge for some students. One recommendation that may help is to keep up with the literature in a given area and read papers on a routine manner as this exercise helps one become better with time. It is very important to read carefully and understand on how papers are structured and arguments are made. Earlier, we used to have two other journal clubs: an Immunology journal club on Tuesday and a molecular biology journal club on Saturdays. These no longer exist and ! we shoul d try to get at least one revived in the BSB. Journal club presentations and discussions are critical for scientific research and thinking and the importance of these are understood by students with time. Every four months or so, we have chalk board presentations by students to summarize their research findings and also to back up all data. Following these presentations, I give an overview of the laboratory so that the success and shortcomings are known and areas that need to be worked on are clear. Importantly, major lab cleaning, defrosting of fridges and freezers, cataloguing of strains, cell lines etc are done regularly. After completing these activities we go out for a lunch. The lab takes “eat outs” very seriously, sometimes too seriously! Often, we go out after presentations etc – I think it has social bonding effects and needs to be encouraged in the interests of a congenial work environment.

The laboratory has also differentiated with time: initially, students would make the breaks and follow them up for their PhDs. These days, majority of the breaks come from studies by older students or JRFs, which are followed up by newly joined PhD students. Consequently, the effective time for PhDs has and will reduce for the smarter ones who are able to capitalize on these breaks. By and large, individual students pursue their interests and the progress is dependent on the student’s skill level, motivation and time put in. The fact that the last two graduate students submitted their thesis within five years is a good sign! It is of advantage to everyone if students work hard, publish papers, submit thesis within five years and move on to their next steps in their careers. It is difficult to learn newer tricks as one ages and it is better for students to move on to another setting within five to six years and acquire newer skills that will make them better scientists and attractive to potential employers. The world has become increasingly more competitive and it is in the interest of students to learn quickly, publish papers, submit thesis and move on to their next steps in their careers.

How does one differentiate an average student (common) from the exceptional student (rare)? Over the years, I have concluded that the exceptional ones refuse to play safe as the PhD degree is not their final destination. They work with passion keeping long term goals in mind, network well, and push themselves and their mentors to try to elevate the quality of their publications – in the process they aspire and become better scientists.

Grants

The first grant that I received was a start up grant from the then Director of IISc, Prof. G. Padmanaban. This money was utilized to buy some key equipments and consumables. The Department had also received a grant as part of a renovation grant on account of the fiftieth anniversary of India’s independence in 1997 and a part of this was used for the civil work to make some of the laboratories functional. This money was used to refurbish dirty rooms into functional labs and there was a small opening ceremony about nine months later by Prof. Padmanaban to declare these labs open. As resources were limiting, Utpal Tatu and I, the two of us who joined as faculty members at the same time, set up a common tissue culture lab – a remarkable venture in an individualistic place like IISc. This tissue culture set up functioned well for several years. In addition, it was a meeting place for “girl meets boy or vice versa” between the labs and at least one match has been known to emerge.

It took me some time to get used to the Indian system of writing grants and the advice by senior faculty was to get going with smaller ones, find the feet of the laboratory before trying for bigger ones. The first grant that we got was from CSIR, a highly efficient organization, was for ~ Rs. 6 lakhs in 1998. The ideas in the grant were the basis for microarray studies proposed to ICMR several years later. The initial CSIR grant was useful because it got work started and we bought our first PCR machine! The grant proposed to identify novel IFNg-regulated genes but we ended up studying the differences in requirements for MHC class I molecules, Kk and Dd, using the H6 hepatoma cell line. The second grant was from DST and ~Rs.13 lakhs was sanctioned in 1999. The proposal was on characterization of Mycobacterial proteasomes; however, we ended up identifying Peptidase N as a major amino-endopeptidase in E. coli. The third grant was from DBT which was sanctioned in 2001 and was useful in performing the T cell activation work. During the initial years, there was some money but not a whole lot. Also, I did not feel comfortable in proposing big projects without any guarantee to deliver.

Subsequently, we were discussing with companies about potential projects. One person who was introduced to me by Prof. Rajan Dighe, MRDG was Dr. Khamar from Cadila Pharmaecuticals. He wanted us to study the effects of autoclaved Mycobacterium indicus pranii (MIP), which had been shown to be effective as an adjuvant together with drugs to combat Leprosy. The company felt that this strain may be effective in other models of disease and were in discussion with DBT with regard to funding. This grant got approved in 2006, our first BIG grant which initiated the second phase of the laboratory and Prof. Surolia’s help is greatly appreciated. Also, this work led to an interaction with Prof. G. P. Talwar, the founder of the National Institute of Immunology (NII) at New Delhi, who discovered MIP. I was impressed by his “joie de vivre”, his eye for art, lust for work several years after retirement and desire to make an impact in terms of translational deliverables. His reminiscences in J. Bioscience (2005) is extremely insightful and sheds light on what it takes to build institutions and about life in the biological sciences in this country. Prof. Talwar has been very supportive of our work, which I appreciate. Later, another project on the efficacy of MIP during sepsis was also funded by CSIR. Both these projects brought in significant money to the lab and helped fund “blue sky” research. Currently, we are collaborating with a company in a DST funded grant to study the effects of molecules that block the production of cytokines and studying their efficacy in vivo inflammatory scenarios. Hopefully, this study may lead to some potential drugs.

Overall, these experiences taught me a few lessons: First, money is absolutely important for driving research for which sustained funding is required. One needs money to obtain preliminary results that are often the basis for larger grants. Once money arrives, students can perform experiments which lead to publications, patents and newer set of preliminary data that can be the basis for fresh grant applications - it is a cycle! Also, it is useful to remember that students are more attracted to the laboratories that are well funded. Second, to get money, one needs to propose the best projects occurring in the laboratory or cater projects to perform work for funding agencies or companies. One should be clear that an eminently doable PhD project may not be the best project to propose for funding. These two are delinked and only the best projects should be proposed as there is intense competition for grant funding. Sometimes, one may need to do an extra project to bring in funds into the laboratory.  At one time during a funding crunch in the laboratory, we did perform a project on Leptospira, a spirochete that causes “rat fever”. Dilip cloned the LipL32 gene which encoded the major outer membrane protein by Leptospira and Pankaj performed the experiments that were done in collaboration with Dr. C. Nagaraj in the National Tuberculosis Institute (NTI), an ICMR organization in Bangalore. Third, once the faculty gets the money, she/he can use it judiciously as long as publications and patents arise. Therefore, if the money is spent wisely, it should be possible to perform the work laid out in the grant and also set aside some money for basic questions that one may like to pursue. There are plenty of examples from my laboratory where some of the best publications arose from studies that were not directly funded by grants. This amount of freedom is required in this business as scientific research is not straight jacketed. However, it is important to! show p roductivity; otherwise with time, funding becomes difficult. Fourth, it is best to keep all options open as it takes time for grants to be processed and financial sanction takes its own course. Also, grants should be focussed and the proposal should go down in depth. Fifth, it is probably a good idea to get students involved in grant writing as it is a useful learning tool, one that they will need to do in the future. The recent initiative to sanction a basal amount of consumables money to all faculty in the Biological Sciences as part of the grant-in-aid funded by DBT is welcome. This allows for a more level playing field in comparison to other Institutes. Importantly, it allows for laboratories to function especially when faculty are in between grants and ensures the PhD work of students is unaffected.

Travel

One of the perks of belonging to this profession is to travel to distant places and countries and communicate one’s research findings with peers and students. Over the years, I have certainly enjoyed travelling to different parts of India, e.g. Bhubaneshwar, Sanchi, Raichuk, Trichi, Vadodara, Vellore, Shantiniketan etc. After the relocation back to India in 1997, my first trip abroad came in 2004. I had decided that it was better to focus on setting up the laboratory instead of going abroad just for the sake of travelling abroad – after all, one needs to have some reasonable data and stories to discuss. This line of thought is distinct from another which states that faculty should be visible, attend International conferences and network with faculty within the field. I recall that from the time I landed in Boston in 2004 and took the metro, the transition to American society was smooth and I blended in well after seven years. Of course, it is nice to meet old friends at the FASEB meeting and others who were living in the Boston area.

The second trip was a trip to Malayasia in 2005. It came about as a request from Dr. Ravindran who was at the Regional Research Centre, ICMR in Bhubaneshwar to accompany him and assist in teaching and demonstrating laboratory practicals in Immunology. I got to see the mix of Malay, Chinese and Indian descendants who make up the population of Malayasia. Also, the remarkable progress that the country has made due to oil in few years was amazing! We had to take breaks at periodic intervals to allow people to pray. Also, most women cover their heads as part of their tradition and religious belief. Best of all, was the food which I enjoyed very much.

Picture 12

My recent two trips abroad came from an unusual travel grant. Several years back in June 2007, I received an email from Grant Lythe at the University of Leeds. He wanted me to speak at a session on Mathematical modelling of the Immune system at a meeting in Hyderabad which was organized by the Royal Society, United Kingdom and the Indian Academy of Sciences, New Delhi. I wrote back promptly explaining that my laboratory works on experimental T cell biology and we did not have an experience in this area – most important, math was not my strong forte! However, Grant persisted saying that this was an emerging field and that I should give it a try. I agreed as it was an all paid for trip to a fancy studio in Ramoji Film city, Hyderabad. I did explain to the delegates that this part of India was all “make believe” and far removed from real India. In any case, I met Carmen, Grant’s wife, who has incredible energy and an enormous capacity to bring people together. She suggested that a joint grant be written and submitted to the European Commission. This grant was funded and I attended the get together at the Los Alamos National Laboratory in 2010. The history on how the atom bombs were built by the group led by Robert Oppenhiemer was educative. In addition, I gave talks in San Diego, San Francisco etc. It felt good to go back to Southern California and the bay area and meet my older Professors, colleagues, family members and friends: Howard Bern, Nilabh Shastri, Gary Firestone, Wendy Havran, Stan Grell, Matthew Krummel, Evan Hermel, Kate Marusina (Picture #12) etc. One of the highlights was walking up the Berkeley hills after all these years – yes, I did it!

Picture 13

This year, I attended the meeting organized by Carmen and other collegues at the University International de Andulacia (UNIA) in Baeza, Spain. It was wonderful to get a feel for the Spanish way of life which is more in touch with my laid back life style. The food, to say the least, was remarkable and we were very well taken care of. The combination of history, talks being held at a palace and being able to present data to top notch scientists in T cell biology made the overall experience a zinger (Picture #13)! This time, I also travelled within England and delivered several talks at the National Institute for Medical Research (NIMR), University College London, University of Leeds, University of Liverpool etc. During my stay in Leeds, the warmth shown by Grant and Carmen was touching (Picture #14). In addition, I learned to cook the “paella” and Spanish omlette! It was my first visit to UK and I liked it: first, the universal health coverage is a great idea. Although there may be some misuse, the concept that every citizen is guaranteed to universal health care from birth to death and universal education are worthy ideas for any civilized nation. Second, the public transport system consisting of trains, metros and buses is excellent. Third, they have preserved the history well and several aspects of the great British Empire can now be found in museums, which are a treat. Fourth, greater London is a great globalized metropolis and I felt extremely comfortable travelling and enjoying the sights. However, the weather in UK made me understand the (primary) motivation as to why the English established colonies in sunny areas all over the world. This grant also allowed two of my students, Manoj and Mukta, to travel abroad and get a flavour of England.

Picture 14

It is important to publish and also to give talks – the latter helps in name recognition as it allows more people to become familiar with your work in a personal sort of way. Life as a researcher allows for travel to different places and one must use it to enjoy the newer sights, meet families, make new friends and also to educate students/faculty about one’s own work.  Most importantly, one can see the directions that certain fields are moving to and one can make course adjustments if needed. Ideas are important and travel stimulates the mind. In fact, I remember my discussions with a precocious student at the NIMR, London. This student kept quiet during my talk but opened up during the one-on-one discussions and came up with some insightful suggestions which Mukta is following up. In addition, he suggested that I visit Kew gardens as he felt that I would like it – this guy is good and read me well!

"Gyan" to students

Let me categorically state that a research career is NOT meant for everyone – just as everyone is not suited to become a poet, a singer, a software programmer, a painter etc – this job is not meant for everyone! A good researcher needs to be interested in academics; however all students who are good at academics, i.e. getting good grades and passing competitive exams, may not be fit for a career in research and become good scientists. This business is akin to a marathon runner – one has to be skilled, patient, learn to multi task, manage people and resources, and above all, have an abiding passion for research that will be tested during tough phases. How does one know whether one is fit for scientific research? The student should be good at academics and clear the entrance tests. Subsequently, some laboratory experiences are essential to figure out one’s inclinations. The combination of these two sentences is the key and, finally, one should try – as they say: better to try and fail rather than not try at all!

There are some points that I tell my students and these may be helpful to others too. I realize, of course, that one can take the horse to the water but the horse will need to drink on its own! In any case, for whatever it is worth, these are some of my “gyan”: first, learn laboratory skills and become technically competent, which are critical for the student’s self confidence. This aspect is especially important for younger students who are making the transition from “book to the bench.” Second, learn to ask questions – it is best to learn by asking questions with respect to your own work as well as work done by others. Attending seminars and trying to ask questions is a good start. One gets better with age and one good question can make all the difference! I have observed that confident students often ask questions and once their confidence level falters, they stop asking questions. Self confidence is the key and the student’s perception on how their project is moving often plays a key role. Third, ensure that your data is highly reproducible and it may be best to confirm it using multiple strategies. It is best to avoid sloppy work and leaps of logic, which are common mistakes that occur during the early stages of a research career. Remember, biological research is mainly experimental and there are lots of variables; therefore, it is better to understand these variables. It is always better to use direct approaches to address the question rather than indirect means. A piece of advice that my PhD advisor gave has stayed with me: if your data is true, put it though the harshest tests; if true, it will hold otherwise not! Fourth, it is important to complete a piece of work and get it published soon, which is the most important aspect. It is important for students to get going on their work soon and I remember my dad’ advice: morning shows the day! Taking too many holidays breaks the work rhythm and slows down ! the PhD process and rhythm of work. While it is important to recharge, it is good idea to plan beforehand and set up work targets that need to be completed before taking holidays. Please realize that it is best for students to publish their projects and not rely on others to complete this job. Fifth, learn to communicate well with respect to writing and talking skills. These will be required for grant writing, research presentations etc. Science writing is a skill that students in India need to pay careful attention to. Even students who can write in reasonable english falter when it comes to science writing. Students should read papers carefully, analyze the structure of the paper and develop a better sense on how to write about their findings. One gets better with practice and it is best to start early and practice makes one better. Do remember to back up your data at periodic intervals. Sixth, develop soft skills (e.g. better interaction, managing people, handling pressure etc) as these are likely to be helpful as an independent investigator. Most likely, the ride will get bumpy and it is important to remain calm and to stay in course!

Seventh, while scientists may be individualist, the fact is that we work as a group. It is important to remember this aspect and it is certainly possible to do well in your own study without antagonizing other members in the group! Also, keep in mind the welfare of others in the group. For e.g., while working with toxic chemicals, radioactivity etc, please take precautions to protect yourself as well as others in the group. If there is spillage, please leave a note and inform others while clean up is initiated. Eight, be aware of the clock and learn to complete projects soon. It is best to avoid distraction and focus completely on the PhD project. There are several distractions here for students – more so with Facebook, Twitter etc. It is important to plan your time well. Certainly, one should have fun but focus on the work and then have fun. It is certainly possible to complete a PhD within five years but it involves a lot of work to get the papers published. Also, there is no point in hanging around for too long after the open defence is completed unless the student absolutely needs to complete some key experiments for submission of manuscripts. Students do tend to relax after the PhD submission and it is only the enlightened ones that realize the importance of papers. Therefore, it is important for students, in general, to “move on” to a new environment after they secure their PhD degree. While doing my PhD, I bonded well with a 6 feet tall and 6 feet broad lab technician and ex-football player (a “jock” in American parlance), Stan Grell, who decoded life in simple terms for me. He felt that it was important to settle down by thirty five years of age. It was good to meet Stan during my trip to Berkeley in 2010 – he hasn’t changed much and is enjoying his life by taking care of his grandchildren. Several places do prefer to hire younger faculty as they will contribute longer to institutions. Students will do well t! o plan a head and to remember this thirty five age rule! Finally, learn to balance work and play. Take care of your health and manage time so that there are avenues for relaxation. Basically, the strength of signal works here too: less time spent on work by students leads to delays in PhD submission whereas too much work may leads to burnout and fatigue. There is pressure in this line of work and one need to have supporting friends and family to go through the periodic ups and down phases. Research is full-time activity and one cannot work half-time – it is all consuming! The fact is that it takes a lot of time and toll on health and family life. I am reminded of the suggestion by Miguel Cruz, a visiting scientist from Mexico, who was my colleague in the University of Cincinnati. In his sonorous voice, he would propound that one word is important in the future for any scientist: B A L A N C E!

The majority of students love their experience in IISc and appreciate it more after they leave the campus. Apart from the degree, I suspect other factors are at work. For several students, this is the first time away from home and their foray into their experience with real freedom away from their family can be exhilarating. Some even find their life partners while doing their degrees. The support network that students develop here plays the most crucial role and plays important roles in their careers later. Therefore, students should make the most of the IISc experience and look back at it when one gets older and the heart gets fonder!

Musings to faculty

How did I realize that I could adjust to academic life? I was comfortable working in a laboratory settings, liked reading research papers, spending time in the library. My brain takes some time to digest information but it works in the background. Also, I am a slow writer, but one has to plod as it is a real challenge to fill an empty sheet of paper with a reasonable survey of literature and discussion on the implications of research findings in a manuscript. Actually, I quite relish the challenge! Both for my PhD and post-doctoral research, my work involved screening for projects, homing and independently working on a few. Also, I have been cautious and adjusted to the situation – “adjust madi”, as they say here! Consequently, it has taken some time to publish but I think we have been right in the final analysis. As an independent faculty, I have followed a similar strategy, which works very well for strong and driven students. From the faculty member’s perspective, it is not an easy job dealing with the idiosyncrasies of individual students as each one is different and needs to be nurtured in a unique manner. Initially, I felt that a professional relationship was sufficient as this works in the West. However, as I have got older, I feel that a “connect” is required between a faculty and students in India. In general, students here are more comfortable and will work better if they are able to “connect” with a faculty. Perhaps, this is true of other aspects of life in India as well, which makes it more unpredictable and exciting – nothing is straight forward in research and life!

It is important to work on research areas that one is passionate about. It is difficult for me to fathom the reasons for doing this, other than the excitement, that comes from self driven desire – perhaps, I am naïve! However, life in research has several lows and few highs and managing these is not easy. There are several times when one goes through low phases: During this phase, it is best to lie low, talk to some close friends and hope it gets better with time. A rebuke or a nasty comment can also motivate oneself to do better provided one is not too sensitive. There is at least one incident which led me to write a paper within a week and submit it to a Journal, and it was accepted quickly too without any major revisions.

Time can be a healer or a destroyer! Life takes its own toll and over the years, I have often seen scientists differentiate with time and become overly cynical. Once this happens, the system has got you and it is a trap that one should avoid. Let me give you an example: during the first few months when we were searching for apartments in IISc, we enquired as to the water and electricity conditions prevalent in a housing colony to a colleague residing there. His reaction was sharp, “Water and electricity here are as good or as bad as anywhere in India. If you don’t like it here, you can go back to where you come from…..” This is the point: when one becomes cynical, it spreads to others and students sense it. The first year of transition from a postdoctoral researcher to a faculty is critical. In most cases, if one survives the first year of adjustment, one is likely to survive and may do reasonably well in the future. Also, the most innovative research leading to good publications is often done by faculty when they are young. As one gets older, middle age catches up, the age gap between the faculty and students increases along with cynicism and the drive slows down as one gets bogged with health and family issues etc. All these issues are a big concern for me and I am trying to figure out avenues to avoid or reduce the problems associated with these common life traps ahead.

One observes different faculty and how they lead their lives, their general state of happiness, their drive, attitude towards work etc. This leads to better understanding of the existence of multiple phenotypes and different paths chosen. Observations are important and each faculty needs to make her/his choices and take appropriate decisions. After having made these choices, she/he should be comfortable with the consequences of these choices. The latter part is the key and better understanding of this simple philosophy will reduce grief in the future. One should certainly try to do the best but there is no point in making artificial or unattainable goals as these are bound to lead to pressures which will have their own effects on students and family. However, it is easier said than done and one differentiates with age and life experiences. Therefore, to sustain in the long run, it is important to have a sense of humour, remain positive and spend time/derive support with a select group of friends. Comparison is the name of the game and one should have a balanced perspective without becoming too sensitive. There is lots happening here and one needs to ensure that the “noise” does not dominate one’s thinking and proceedings. One form of therapy that works for me is to work along with students as it does enthuse them. I do the oral injections in mice and it makes me feel useful. Also, the trip to the Central Animal Facility helps me to monitor the mice experiments and spend time with students. It is useful to “connect” with students: one needs “young eyes” and “young minds” to take closer look at data, typos in writing, bouncing off ideas to come with fresh perspectives, keep up with rapid changes in sciences, communications etc. For the students who try your patience, it is useful for the faculty members to remember that to help oneself, sometimes one has to help the student. Again, it is easier said than do! ne!

In addition, it may also be helpful to have a number of projects in the laboratory – a little diversity may be useful as projects work at different rates. Too much specialization or dependence on a particular equipment or a student may lead to hitting a wall sooner or later which can be counter-productive.  Here, too, the strength of signal is important: relying on a single specialized project can be a problem in case it doesn’t work out very well whereas working on too many projects may result in too much breadth and lack of depth! Perhaps, a middle path is the best solution. Also, it is best to see the raw data as it is generated by the students during weekly meetings or during lab meetings. A faculty should be careful about research studies done by students and ensure that the studies are reproducible. Patience is another quality that one develops with age. In case of dealing with students, this is often very useful as each individual peaks at different time points. In case of problem cases, it is better to be patient and see how it works out. In some cases, students go through various phases before getting back on track. In case it doesn’t work out, matters are taken to their logical conclusion but it is better not to rush with these cases as “haste makes waste”!

The initial phase of work in the lab focused on PepN but now we are more involved in understanding the host response during infections or tumors using in vivo systems involving mice. Perhaps, it helps to remake one-self at periodic intervals. One needs to adjust to changing conditions, find alternatives and move on – “adjust madi” or flexibility works. Prof. Maheswari had a stroke a few months before his retirement, which led him to use the wheel chair. However, he remains active and has contributed in a positive manner by writing books. One needs to recall these stories to remain positive. All said and done, it is important to do well as “success breeds success” and motivates both faculty and students. It is important to remember that the most important determinant of self esteem among faculty members is the quality of research work being generated in the laboratory – all other tangibles are peripheral! If one’s research moves at a reasonable pace and one keeps thinking about experiments and results, faculty tend to be happy with their work.

It is certainly possible to do excellent work here and some factors have been identified: First, good students are a key. Often, interesting observations are made by them and followed up. Do remember that it may be best to spend time with students when they are in their early phase of their career, i.e. the first two years of the PhD program. Like kids, it is difficult to mould students at later stages of their graduate education. Once students get an early break and feel set, chances are high that they will remain motivated and complete projects in time. To get the work published in a better journal, synergistic collaborations are required and these may be within or outside the laboratory. I strongly feel that in the interests of better publications, it is very important to get all “all hands on the deck” for the final push into a GOOD journal. Faculty need to try to enhance the quality of their work and its gets tougher with age, which is a real challenge! Second, it is important to set up an atmosphere in the laboratory that fosters collaborations. It is great when two or more students come together and work towards a greater goal. Third, infrastructure and facilities are important. In the pursuit of “blue sky” ideas, technology often plays an important role to get better insights into results, e.g. array and imaging facilities. I prefer to work on the biological aspects and then use technology for the push rather than the other way around. It is possible for both strategies to work as they are not mutually exclusive. One of my favourite strategies is to use screening methods to identify novel observations. For example, the initial observations with PepN were made using different peptidase substrates. Also, the preference of PepN for small and basic amino acids was deduced from screens. In fact, our recent publication on chemokines stemmed from a screen that identified Ccl3 to be down regulated by IFNg. Fourth, research is driven! by mone y: purchase and maintenance of equipments, consumables, skilled research personnel etc. While money is clearly important, it is also important to come up with good ideas and have people who enjoy working in the laboratory. Often, I feel that it is better for faculty members to be given a certain amount of money on a regular basis to focus on their research work so that they don’t have to worry about running for money at periodic intervals. I realize that some of this may be wasteful but it can be linked to generation of PhDs, research papers published in the past few years. Fifth, it is best for the study to be supported by different strategies, e.g. a combination of genetics and biochemistry. Right now, we have been using in vitro and in vivo approaches to explain possible physiological situations to make the story stronger. It is useful to remember that the possibility of a small molecule that has therapeutic implications catches the attention. Sixth, it is obvious that projects need to be completed and the studies published. However, in some cases, students get demotivated at the later stages or leave after submission of their PhD thesis; consequently, it is left to the faculty to ensure that the work gets published. This is a challenge and one should ensure that younger students or JRFs are able to pick up these projects, ensure that the results are reproducible and get the study published. In my laboratory, some of the projects initiated by the senior generation of students were completed by the younger generation of students. Seventh, regular turn over of students at periodic intervals is a good idea. After a point, the efficiency of senior students in the laboratory tends to sap, similar to the stationary phase in a growth curve. Therefore, infusion of young minds and fresh energy at regular intervals is required. Eighth, a faculty member’s responsibilities puts on a lot of pressure and a support network of family and friends are required to c! ushion t he periodic pressures and this aspect needs to be underscored. Each faculty needs to find avenues to relax and recharge batteries, e.g. taking trips, hiking, yoga, exercising etc. Finally, a little bit of luck is required for all the players to work in harmony and get the job done. However, it is important for faculty to do well to sustain their self belief and feel that they are a part of the peer group.

Other activities

Somehow, I have managed to get myself involved in several activities here and I will elaborate a little on some of them. It is good to get involved in these activities as it exposes us to different experiences, meeting different people and makes life more exciting. However, these activities should not come at the expense of the laboratory’s research interests or affect the pace of work in the laboratory, which is the main reason for us to be here. I find that only a sub group of faculty members are involved in other activities. I do wish that a larger group is involved as it is important for majority of the faculty to feel that they are involved in some activities of the Institute. Some faculty are amazingly good at managing these activities plus their lab and I tip my hat to them. Also, one’s students also get involved and not all students can manage several activities and responsibilities. Thus far, my students have got involved in my activities but they have been patient with me.

Picture 15

Molecular Immunology Forum (MIF): The MIF started off as a rebel group by younger Immunologists several years back in 1993. The idea is to have chalk board presentations and “talk” about work without relying too much on slides. The ideas behind the work and problems are more important than actual data and publications. Prof. Manjunath introduced me to the group at a meeting in Bangalore in 2000. I presented Sam’s preliminary observations and the responses were different: Satyajit Rath (from NII, New Delhi) liked the work but Vineeta Bal (from NII, New Delhi) noted that it was all observational and without mechanisms (she was right!). Subsequently, we did try to understand the mechanisms and Satyajit Rath was extremely helpful in reading our manuscript quickly and suggesting key changes in the language and tone of the manuscript that ultimately led to our first publication in J. Leuk. Biol. in 2002. Experiences make a lot of difference and productive suggestions are very useful, especially during the initial years as a faculty. I do hope this trend continues and I have been attending these meetings every other year or so. It has been good to visit different locations in India and be a part of this support network (Picture #15).

Fluorescent Activated Cell Sorter (FACS) facility: The procurement of the first FACS machines in IISc coincided with the year of my joining, i.e. 1997. However, these were installed in 1998 as it took time for site preparation. In addition, time was taken up for repair as rats had eaten up some electrical wires in the instruments during the storage period. Prof. Nayak and Prof. Shaila were instrumental in setting up this facility and several of us are thankful for their initiative and efforts. Dr. Omana Joy has been with the facility since 1998 and she has been instrumental in trouble shooting with students and helping the facility. I became Convenor of the FACS facility in 2006, Dr. W. Surin was appointed as a Scientific Officer in 2008 and there are two JRFs, Pooja and Kavya, who are the operators (http://mcbl.iisc.ernet.in/facilites.html). Overall, the FACS facility is one of the better run facilities and it works with minimal faculty interference. In general, the facility runs on auto-pilot and the activities of the facility are overseen by a Committee that oversees purchase of equipments, hiring of personnel, discussions on complaints etc. This is not to say that there have been no problems but they are sorted out as they arise. The sheer number and diversity of samples handled by the FACS facility is impressive. Lately, several laboratories from other Divisions in IISc are increasingly using this facility which is a good sign. Perhaps, it’s time to upgrade it from a Divisional facility to an Institute facility.

Picture 16

Conferences: I had no experience in organizing conference before 2010 and frankly no desire too as I felt research work in the laboratory and publications are clearly more important. However, I had heard from seniors that organizing conferences does give enhanced visibility at national and international levels which may be helpful during one’s career. In any case, Prof. Nagaraj asked Parag and me to help organize the Society of Biological Chemists (SBC) conferences in Bangalore in December 2010. I had noticed that the “buddy” system works well in inviting speakers for conferences: if you invite me for your meeting, I will invite you for my meeting. In a significant move, speakers were short listed for talks based on papers published in the past two to three years and these were approved by the Scientific Advisory Committee. Organizing a conference for ~800 participants is not trivial, but the support from all faculty in the Division of Biological Sciences was overwhelming. Also, the infrastructure is in place in IISc to hold large meetings: large auditoriums, guest houses, large empty spaces to host lunches and dinners etc. Of course, whenever there were problems, there was a lot of help as Prof. Nagaraj, Prof. Varshney, Prof. D. N. Rao were very experienced and helpful. The staff members in the SBC(I) office, Maitri and Ravi, were very helpful too. We included cartoons and gave a touch of color and art in the Abstract book and banners. Also, there were two entertainment shows, one a jazz fusion music and the other a Yagshagana event, which was a huge hit! Somehow, the meeting went on very well without any major hiccups. Importantly, there was a “feel good” factor during the meeting which was well appreciated (Picture #16). The meeting generated funds for the Society and it is, perhaps, a good idea for the local chapter of SBC(I) to organize such meetings at regular intervals. The only “odd&rdquo! ; part w as that Parag, the Co-convenor, was not present during the entire meeting as he had to go to Mumbai for personal reasons a day before the meeting.

Picture 17

The next year, the Theoretical and Experimental Immunology (TEI) meeting was organized in August 2011 (Picture #17). This was part of the European Commission grant that Carmen and others had secured. It was my first experience in handling an international meeting which was held at the Faculty Hall, IISc. Prof. G. Rangarajan from the Dept. of Mathematics was very helpful and his staff members at the IISc-Mathematics Initiative office were exceedingly competent. It was good to have talks from national and international scientists and the best part was to see the hall almost full at 9:30 am which is early by IISc standards. An important aspect was that Carmen managed to get a wide array of faculty involved to submit another grant to the European Commission.

Picture 18

This year, Prof. D.N. Rao asked me to organize a talk by Prof. Doherty, a Nobel laureate. Now this meeting was organized by the Nobel Foundation, Astra-Zeneca and IISc. The Nobel foundation had a list of requirements and they took their jobs very seriously as their representatives arrived a few months earlier to survey the auditorium, conference rooms etc. The pharmaceutical company Astra-Zeneca also got into the mode and had several people coming in for meetings whereas IISc was represented by only the public relations officer (PRO) and I. Overall, the March 12, 2012 meeting was a big success as students liked the close interactions with Prof. Doherty. It was nice that Prof. Doherty could visit the laboratory and the students enjoyed this interaction (Picture #18). The video of the Bangalore visit by Prof. Doherty can be seen on the Nobel foundation web site: http://www.nobelprize.org/nobel_organizations/nobelmedia/s_partners/astrazeneca/lecture_events/march_2012/index.html
 
I had started out by stating that I had no desire in organizing conferences but to my surprise I found that I had a flair for it and enjoyed the process. It is useful for students to attend conferences and be a part of the organization and scientific activities, e.g. presenting posters, delivering talks etc. Hearing good talks from “stars in science” does have a positive effect on young minds. However, conference organization does take a lot of time and it is best not to overdo it.

KVPY: The Department of Science and Technology (DST) started an initiative some years back to encourage young minds to take up science as a career by offering 10th and 12th standard students scholarships to go into basic sciences. IISc is heading this effort and Prof. N. Mukunda was the first convenor of this program known as Kishore Vaigyanik Protsahan Yojana (KVPY). Interested students should learn more about the program by looking at their web site: http://www.kvpy.org.in/main/. I like Prof. Mukunda a lot, his gentle demeanour combined with an ability to get people together and get work done is striking. Also, I met others through this program, e.g. Prof. Anil Menon from the Instrumentation Department who has been most helpful to me and my family. Initially, we had to help with setting up question papers, interviewing students etc. Overall, I think some students do benefit and several of them enter the IISc undergraduate program or IISERs through this avenue. Organizing this on a national scale is no mean feat and the efforts of several faculty members who take a lot of effort in running it smoothly.

Undergraduate program (UG-IISc): In August 2011 the first batch of undergraduate students enrolled in IISc (website: http://www.iisc.ernet.in/ug/). There were several discussions on the usefulness in starting this program and faculty were divided (as usual). While it is true that teaching is noble and useful, research is tough and competitive. One line of thought was that by focussing on teaching, one can lose the “edge” in research. The counter argument is that there are some researchers who are also excellent teachers. The counter-counter argument is that this does not apply to vast majority of faculty and doing experimental research under Indian conditions is challenging. This can go one and my feeling was some students would benefit from the education and experiences in IISc; also, part of our job here is to educate students. The practical considerations in running an undergraduate program were a bit scary but then the decision was taken at the top. Prof. Umesh Varshney has put in a lot of effort and I have helped him. It has also been useful for me to learn from him at close quarters. There were at least four big issues before starting the Biology part of the UG program: First, majority of the students would not have Biology in their 11th and 12th standard and we were unsure on how the students would respond to this subject. The fact is that biology teaching in schools is often boring and memory based. Second, the laboratories had to be set up, the site had to be prepared and instruments had to be bought. Third, faculty needed to be cajoled to teach UG courses and teaching UG students would be different from teaching graduate students. Fourth, the laboratory practicals were a big concern as constant overseeing would be required.

There is some clarity on these issues as the program is now a year and half old. Several of the UG students liked Biology and have opted for it as a Major (22 out of 83 students, second only to Physics which has the largest share). The big difference has been the faculty, the young Instructors and graduate students who are present in the laboratories. UG students have been able to relate to these young teachers as some bonding is important. Although there was some delay in setting up laboratories, these have now been set up and are functional. The practicals are overseen by faculty, Instructors and Junior Research Fellows are present all the time to assist students. In addition, graduate students act as teaching assistants which is also useful and helps in bond formation. Overall, I enjoyed teaching UG students although some adjustments were required. The focus was on imparting the basics of Immunology with emphasis on innate, B cell and T cell biology. Some applications and historical titbits were added to garnish the lectures. As the number of UG students increase, the needs for teaching assistants will also increase. It is useful for graduate students to teach as it gives them an experience and a feel for teaching. It feels good to interact with the young bunch although they are a demanding lot – and why not? I do think a fairly significant number of UG students will take up research as a career in the future and this will make the program worthwhile. Also, the UG program allows IISc to differentiate into a more University mould compared to that of research institutes and the increased number of degrees awarded may help it get a better global rank.

Planetarium lectures in Biology: Several years back, I met Prof. Vishveshwara at the Dasera music get together of my son Jaidev’s flute teacher, Guruji. Prof. Vishveshwara has been instrumental in building and running the Jawarharlal Nehru Planetarium in Bangalore – not an easy task! He felt that an outreach lectures in Biology would be useful for the community of students in Bangalore who are interested in research. Also, these lectures should not be the tutorial type but should enthuse students into research. There was an existing model in Physics which was working well and the same model could be used for Biology. The program was set up and my job was to arrange for talks by faculty as a module. During the initial years, IISc did assist with a small grant but it has not continued. Now, faculty and sometimes their students give talks on Saturdays. I find that young students are often enthused by talks from graduate students with whom they can relate better. One of the problems, initially, was for students to come for the lectures on both Saturday and Sunday. Now lectures are held only on Saturday and the number of students attending these lectures has stabilized to about twenty-five which is reasonable. Some of these BSc and MSc students have secured admission in prestigious Institutes of higher learning and the program has had some impact. The support from the Planetarium faculty and staff, e.g. Prof. Shukre, Dr. B. S. Shylaja and Mr. Madhusudan, has been most helpful. Community outreach is good and I hope this program is helpful in motivating students to take up research as a career.

NPTEL stands for National Program in Technology Enhanced Learning. The basic module is for teachers to put their lectures along with slides up on the web. There are about forty lectures on a subject and it is accessible to everyone on You-tube. Prof. Manjunath, Prof. Anjali Karande and I have recorded several lecture modules on Immunology. Mani helped me with the slides and the recordings were done in the early part of this year. It took sometime for me to get adjusted to this technology and I may come across as “wooden.” The fact is that I very much like the class room format which allows for interactions with students. Learning needs to be a two way process and there is a lot of value to be attached to the class room experience. Otherwise, there would be no need for class rooms as students could learn from text books or from pre-recorded video lectures on the web. However, these lectures may be useful as “adjunct” teaching resources instead of completely replacing the class room teaching learning process. It appears to be useful to some students based on the feed back from emails. Interested students in Immunology may look up this course as there is a lot of useful information: http://nptel.iitm.ac.in/courses/104108055/16

Major phases
Picture 19

Overall, there have been two phases in the lab until now: 1997-2006 and 2007-2012. The initial phase was one in which systems were developed and some successes were achieved. As resources were limiting, it was harder for the first bunch of students but systems were set in place although it took time. The second phase saw an increase in funding and the experiences from the first phase taught us a few lessons which led us to become more adventurous. This phase was especially helped with the establishment of the mice knockout facility and I need to express my thanks to R. Manjunath and Anjali Karande. Getting facilities off the ground, especially those involving animals, is not easy and it must have been difficult in IISc. However, the members of the Central Animal Facility, including S. G. Ramachandra, Rosa and others, have worked hard and need to be congratulated for getting this initiative off the ground. It has made a difference to our laboratory as it led us to investigate the in vivo relevance of some of our in vitro findings. The initial findings from our laboratory using knock out mice in the infection and tumor models were accepted forpublication in 2011. I was happy with the two papers that were accepted in 2012 end, one in Immunology and the other in Journal of Infectious Diseases - perhaps, they portend better days in the third phase of the laboratory beginning in 2013.

Picture 20

After all, we need to be positive and hope that our research will make headway in previously unexplored areas. The current atmosphere in the laboratory is also more positive and labmates initiate plans on their own, including some experiments, eating jaunts and trips. Some recent initiatives that were initiated by lab members on their own were getting T-shirts printed denoting fifteen years of the lab (Picture #19), lighting lamps during Diwali in the corridor of our laboratory (Picture #20) etc.

Epilogue

This essay started off as a short piece but has now evolved into a much longer write up than I had originally intended. I hope the readers will get some insights into the laboratory and life here: the interactions, some ideas on how projects were initiated, the limitations in setting up and running a laboratory etc. I have written about the highs and lows and, in keeping with my style, resisted the temptation to sugar coat! It is certainly not a mainstream experience, it is more likely to be an off centre piece. I have asked myself whether this piece will be at all useful. Perhaps, along with written memories of other faculty members in Biological sciences here and other institutes in India, it may constitute a part of the collective experiences during the phase of increased opportunities for biological research in India beginning in the late 1990s and early 2000s.

In the next phase, our research studies will need to have more impact and, perhaps, shed light on possible translational strategies. Along the way, more students should learn newer skills and also enjoy doing research. Sustaining good learning in an amiable environment, together with making a greater impact in terms of research, will be some of the key challenges in the future for the laboratory. Like wine, I am hopeful that the laboratory will get better with age!

Dipankar Nandi
December 2012

 

Acknowledgments
I greatly appreciate and thank Vrinda Nandi, Utpal Nath and B. Chetana for their patience in reading this rather long write up and recommending editorial changes.