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GENERALS OF THE SIGNALLING PATHS

Singapore, a globally-acclaimed environment conducive to financial and business operations, is now gaining well-deserved respect for fostering scientific research and attracting leading scientists from all over the world. Dr. Dmitry Bulavin chose Singapore over one of the world's foremost medical research centres and moved here about six years ago, upon the advent of governmental efforts to support the science. Now, he is a Senior Principal Investigator (Associate Professor) at the Institute of Molecular & Cell Biology (IMCB). Dr. Bulavin was named by Senior Minister Goh Chok Tong among the Russians who contribute the most to Singapore's development.

Dr. Bulavin, why did you move to Singapore?

I worked for over five years at the National Institutes of Health in Bethesda, near Washington D. C., where I was a staff scientist, which is a safe, permanent position. However, I was only semi-independent in my work, while wishing for more independence and changes in life. I sent my resume to Singapore and was offered the position of head of the lab. Currently, I have seven people in the lab, with plans to expand the staff count to 10.

Why Singapore? First of all, I do not like snow and cold, and Singapore is very comfortable and clean. I instantly liked it and adjusted very well. I do a lot of scuba diving, so this was one of the reasons, too. I really wanted to explore the region, for I like Asian culture.

Secondly, and most importantly, Singapore was a really interesting place to be in because back then they had just started to invest a lot of money into research. I joined the IMCB two months before we moved to this building [Proteos Building at Biopolis N. M.]. At that time, the IMCB was still under the National University of Singapore, and later became part of the Agency for Science, Technology and Research (A*STAR). It was exciting to be exactly at the epicentre of the changes.

Genetic research is extremely expensive. In America, where all research work is funded through grants, you have to go through a long and difficult selection process. Because of the high costs involved in research, you need to apply for several grants. Singapore is one of the very few countries where research is budgeted, which is of great help and gives a certain freedom within the allocated budget. As a part of A*STAR, I an use all its facilities that keep appearing. I pay for it but, as a member of the A*STAR, I enjoy special discounts and have full access to any facility.

Is it rewarding to work in a multinational environment, or does multiculturalism affect mutual understanding?

I like to have people with different cultural backgrounds in the lab, so I am trying to recruit globally. However, the priority lies with a person's previous experience rather than his / her nationality. I have absolutely no inclination towards having more Asians or Caucasians. Now, I have Singaporeans, a Russian, a French, an Indian and a Chinese in my lab, which is great. When coming to Singapore, be prepared to embrace cultural differences, otherwise it'll be too hard for you. Personally, I was apprehensive at first, expecting the local culture to be very different from what I was used to. But I idn't have any problems whatsoever it has always been an enjoyable experience. I ven became a permanent resident.

Your recent discovery of a new role for p38MAPK (p38 mitogen-activated protein kinase) in ageing has been widely acclaimed in scientific circles. 103rd Meridian East is targeted to the general public. Could you explain the nature of your discovery in layman's terms to our readers?

We do not specialise in ageing per se. We deal primarily with cancer, trying to find ways to prevent and treat it. But a particular gene we were working with had something to do with ageing, so we decided to explore it further. Different cells that form our organs have specific functions. They age' over time, accumulating irreversible changes, which prevent them from functioning properly. For example, the cells forming the walls of your blood vessels accumulate these changes, become more fragile and, at some point in time, may break and result in a stroke.

The changes in the cells are so prominent that they are able to tell us if a cell has lived a long life and if something is going to happen to the organ soon. Several prior studies showed that gene p16 is one of the molecules that execute' the final decision for a cell to live or die. However, it wasn't clear how exactly this execution was regulated. What we found is that the p38MAPK regulates this process. If something happens in a cell, it activates p38MAPK, which, in turn, activates p16 to tell the cell it is time to die.

We found out that this signalling pathway regulates the accumulation of changes in a cell, so if the signal is disrupted in the pathway, the ageing process will be delayed. Of course, the cell still continues to age, but you may prolong its life.

What could be a ractical implementation of our findings?

There are few directions to continue the research. The process I have just described is typical for differentiated cells, and we want to know whether it happens to the stem cells that give rise to differentiated cells. For example, in an older person, regeneration takes longer than in a young one. The reason behind it is that the stem cells in an old organism are already affected and not efficient enough in terms of regeneration. We want to find out if the same signalling pathway is applicable to stem cells.

Another issue is related to cancer. One of the ideas is that we fail to cure cancer because we treat it as a disease of cancerous cells, forgetting that it is the also a disease of the environment, in which the cancer grows. We want to know how cancerous cells interact with the environment, how the environment ages. What we could try doing is to keep the environment of an organism young, which is known to reject cancer.

However, we are a purely scientific laboratory, so our goal is not to create a drug but rather to understand what's happening, share our findings with scientific community including different pharmaceutical companies and help them with further research. There is growing interest from the pharmaceutical industry, so if everything goes well, they will make a commitment.

We found out that this signalling pathway regulates the accumulation of changes in a cell, so if the signal is disrupted in the pathway, the ageing process will be delayed A*STAR (Agency for Science, Technology and Research) is Singapore's leading government agency dedicated to fostering world-class scientific research and talent for a vibrant knowledge-based economy.

Established in 1991 as the former National Science and Technology Board, A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences & Engineering. www.a-star.edu.sg
By Natalia Makarova

 

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