ComCom: Dr. Ghosh, Can you please give us a brief background of your current research work, although it may be very difficult to understand. by most of us....?

My research focuses on two broad areas: We look at the regulation of gene expression at the level of messenger RNA synthesis from the genetic material DNA. Genes are expressed by a set of proteins known as transcription factors. Roughly half of human genes are expressed all the time as the final protein products of these genes are essential for our survival. The other half are expressed temporally and their expression is controlled by inducible transcription factors. We are working on one such inducible transcription factor known as nuclear factor kappaB (NF-κB). Genes that are regulated by NF-κB profoundly affect our immune systems among other functions. In our laboratory, we try to understand how NF-κB activity is regulated both by cellular as well as environmental agents and how active NF-κB in turn regulates its target genes.

The second project in the lab is designed to understand another essential phenomenon called splicing. Splicing is closely linked to transcription. Most of our genes are interrupted, i.e., the genetic information is not linked contiguously. Therefore, transcription factor generates a long mRNA which we call pre-mRNA, which must be processed into the correct form where all the information is linked sequentially, and the non-essential parts are removed. This whole event is called splicing. Like transcription, the process of splicing is a complex event, which requires a number of proteins. We are studying the function of only a subset of these essential factors.

ComCom: What are the immediate and long-term goals of the research studies being conducted in your laboratory?

I am a biochemist and my research focus is to understand the mechanisms of transcription and splicing at the molecular level. It is important that the geneticists properly describe biological phenomena before one can ask mechanistic questions at a molecular level. In NF-κB research, we ask detailed biochemical questions to know the precise function of NF-κB, the components that affect NF-κB function and their mode of action. We hope that answers to these questions generated by test tube experiments can be further verified by animal experiments. We might undertake some of these animal studies in future. Our long-term goal is also to understand the origin of different human diseases that are now only casually linked to NF-κB. One can then rationalize if NF-κB can be targeted for drug design.

Although our long-term goal in splicing research is the same, our current short-term goals are slightly different. The field of transcription is far advanced at the level of living cells. In contrast, we are just beginning to know the players that carryout splicing. Molecular geneticists working in this area must elucidate all players involved in splicing and their biological roles before we ask mechanistic questions. Indeed, we are doing cycles of biochemical and biological research in our own laboratory to put some of the key players of splicing in proper perspective.

ComCom: Why did you choose to pursue a career in biosciences research and why in this particular branch of study?

Most of the time things just happen in ones life. In my case nothing was really planned. It just happened! I majored in chemistry in BS and then in biochemistry in MS. Naturally, I became more attached to biochemistry. During my Ph.D. I decided to continue in the area of molecular biochemistry. I was seriously thinking of changing my field to a more biological area for my postdoctoral research. Then one day I decided to move to an x-ray crystallography laboratory. I still cannot say what motivated me to make such a move.

Over a year into my postdoctoral research things were not progressing as expected. I was desperate to change my research topic. At that time a friend of mine introduced me to NF-κB. I felt that NF-κB was a fascinating molecule, which had a direct impact on human health. So I chose to study it even when my advisor was reluctant about it. The more I learnt about this molecule, the more I became fascinated by it. Ultimately NF-κB became the cornerstone of my research program. I took on splicing only recently. Again, I am fascinated about the complexity and the precision of the splicing process. So much is still unknown in this field. The questions are clear to all of us. The issue is how to find the answers. This is what we live forto find the answer.

ComCom: What tools or technological advances, if any, have been important in your research?

One of the major techniques we use for our research is x-ray crystallography to visualize proteins and protein complexes. Elucidation of molecular structures is key to the design of mechanistic biochemical studies. Structure determination used to be a very lengthy and difficult process. Over the past 10 years or so significant technological developments have made crystallography an approachable method. In particular, an increase in the number of synchrotron x-ray sources, faster and cheaper computers, better programs for structure determination, better methods of protein production have made x-ray crystallography a lot easier. More importantly, a new generation of young scientists are attracted to structural biochemistry. All these will have a long lasting positive effect on biological sciences.

ComCom: Do you expect and aim that all the work conducted in your lab would become highly cited, referred for further studies and technical advancement?

Of course! Science is a collective effort. Each laboratory contributes only a small piece to a big puzzle. Every scientist expects that his/her work will help others in shaping their research in further advancing knowledge. No observation has any significance in science unless it adds to the existing knowledge or originates a new concept. Consequently, original observations are cited by others. Good science has high citation even if in some cases it takes a longer time before others recognize its true value.

ComCom: What are the larger implications/applications for the findings of your research?

Our research has contributed to enhancing current knowledge in gene regulation. Although we have not made any major breakthrough that has changed the current dogma, we have definitely added more to the details. More importantly, our description of the molecular architectures of proteins indirectly helps others to design experiments that they would not have done otherwise. In the same breath I am sure our publications would have prevented some others from pursuing futile experiments. However, I do not feel that so far our findings have made any impact on the cause or cure of human diseases. Well, our work will continue and hopefully someday we would find something truly remarkable.

ComCom: What are the social implications of your work, if any?

I do not think our work has any direct social implications.

Some personal questions,

ComCom: What factors or circumstances led you to academic studies in chemistry at graduate/ undergraduate levels?

I knew when I was in sixth or seventh grade that biochemistry would be an important subject to study and one might make scientific discoveries and be very famous studying biochemistry. Of course I knew nothing about the subject. But my elder brother who was a chemistry major in a college in Calcutta, used to tell me the stories on research done by Dr. Khorana. He told me how Dr. Khorana used his knowledge of chemistry and made remarkable contributions in the field of biochemistry. According to him chemical approach to biology allows one to make great discoveries on living materials. Although, I was a decent student in science and mathematics, I had more fun studying history and geography. I guess eventually when the time came to make a decision, I had to choose chemistry over history or geography, because I was not strong enough to defy my father or teachers. Also, I was interested in chemistry/biochemistry and so it was not an agonizing decision.

ComCom: What motivated you to come to the United States for further studies? When did you arrive here and the steps taken to reach your current levels/ goals?

Honestly, things happened in my life in a rather strange way. Although I had a half-hearted desire to be a scientist since I was a young boy in a very remote village in Bengal, I wanted to do too many things and never took any step to achieve any specific goal. I did not enjoy my college life in Calcutta. My life in a big city was suffocating. Although I had a better time during my masters, many things I saw or felt made me unsure whether an academic career was right for me. I was thinking about starting a business or pursue an acting career. I even thought about joining politics. However, I had a professor who had a positive influence on me. He convinced me that I could be a good researcher. Of course my brother was very encouraging too. My parents did not put any pressure on me. Then opportunity came to go abroad to pursue Ph.D. In India, back then in mid- eighties, there was no opportunity to do real research as a bachelors or masters student. Therefore, I was not sure if I would like to do experimental science or even be any good at it. My doubts disappeared as soon as I joined graduate school. I worked for an amazing scientist during my Ph.D. She was a great scientist and even a greater human being. My lab-mates and neighbors in the institute were good too. I enjoyed being in the lab every minute. More importantly even when experiments did not work (which happened frequently), I did not mind giving it another shot and yet another. My postdoctoral advisor was also a brilliant scientist and an honest person. These are the people who indirectly shaped my life as a scientist. Honestly, I did not think too much of getting a job and having a career when I was a student. Only near the end of my postdoctoral research, when I found out that some of my friends were getting academic positions, I became keen on finding an academic job and believed that I could be a mentor. Well, I found a joba job that I really like!

ComCom: How do you compare or your advice to put India back on the to rails to create a mark in the international arena of scientific research?

The quality of biomedical research in India is getting better every day. I see a group of young people who are doing extremely well. I know some others who are brilliant scientists and doing their best. Although, I am optimistic about Indian science, clearly there are problems at different levels. I know a few heads and directors who are aware of a lot of these problems and are taking the right measures to solve them. Like all other problems in India, our problems in life sciences research are rooted at two levels; socio-economic and political. Socio-economic problems deprive too many people from doing science. The most vivid example is the participation of women in science. If you look at the number of women from high school to college to Ph.D. to independent academic scientists, the number keep decreasing dramatically. Our social structure still discourages women from having a career. Parents and relatives think that raising a family is a higher priority than a career. Even the motivated and talented women, after overcoming family problems, often face a hostile scientific environment where prejudiced male scientists are often too overbearing. This must be changed. We could do much better if 50% of our talent is saved. Moreover, in my opinion, in spite of the quota system, our science is limited only to people from the middle class to the rich belonging to upper caste. Even that is limited only to a few states such as Tamil Nadu, West Bengal, Kerala etc. I can go on and on to point out all the problems. Solutions are also easy on paper but more difficult to implement in reality. We must take a good close look at the problem as a country and need a long-term policy to make these changes.

One can also identify the immediate but solvable problems. These problems are acute and are well known to the scientific community. Here I shall mention only a few. Some old guards (chairs or directors) are much too powerful. Too much power in the wrong hands can be disastrous. It often fosters many institutional policies that are wrong, such as the recruitment of their own candidates at the junior level. These are lifetime appointments, and therefore a mediocre appointment can have a long lasting negative effect. This brings the second problem, which is that the appointments are permanent. We should have a tenure system in India like here at USA. This will keep the young scientists under pressure to be innovative. One must earn the right to hold a position long-term. That brings the third issue, which is that the junior scientists are not given full freedom. Their lives are controlled by the chairs/directors. The juniors should be given sufficient startup funding and personnel support and be left alone to pursue challenging problems. Only then can one evaluate their performance after a stipulated period. The main issue here is to create an environment so that talented young people thrive and the mediocre are purged out. Also regional rivalry often paralyzes science. I see a lack of communication between scientists living abroad and scientists in India. Finally, in spite of good intentions, bureaucratic red tape often slows scientific progress. Here the solutionsrecruit better candidates in a democratic fashion and give them more freedom and make them feel equal to the others who are already there. Rather than competing with others for more power and glory, help each other with ideas, instruments and reagents. Relationship between students and professors must be improved so that students feel that they are colleagues rather than subordinates. While the government is doing a commendable job, I still feel that it can make things move faster. Scientists trained abroad should seriously think about going back to India and those who decide to stay abroad should play a positive role in Indian science. Having said all this I already feel a change in the air. Parallel to many other developments, biomedical science in India is clearly changing for the better.

ComCom: What is your "take-home message" for Bioscience students in India?

The most important thing in life is to know what one likes to do and not what others like one to do. Often in India, we like being told by others what is good for us. Unfortunately, these days a lot of students who are studying bioscience are truly not interested in the subject but they are pursuing it because there is currently a craze about it and their parents made them do so. To them my suggestion is that I hope that the subject grows on you and you become passionate about it. And to those who are truly interested in studying the subject I hope you stay on course even when times are tough. Hope you approach science with real passion and not for money or glory. Money and glory will come if you do it right. Scientific research is not about doing a job but living a dream. Each of you has the potential to do well. Hope you follow the right path to live that dream.

Thank you, Prof. Ghosh, Thank you for your valuable time...... Our Best wishes for the success of all your Research efforts ......

Contact: Prof. Gourisankar Ghosh, University of California, San Diego, Department of Chemistry and Biochemistry, Natural Sciences Building, 9500 Gilman Drive, MC 0375 La Jolla, CA 92093-0375 Phone: 001- 858-822-0469 E-Mail - gghosh@ucsd.edu Webpage: http://www-chem.ucsd.edu/Faculty/bios/gghosh.html