A few Nobel Men

As kids, we study a wide range of subjects in school, from English to Social Studies and Science and even Music and Dance. But as we progress to Senior School, we choose a specific “Group”, be it Biology, Commerce or Computer Science. When we move into college for graduate and post graduate degrees, our education becomes still more specialized. We dig deeper into a specific subject and soon reach a state where we forget the basics of the other subjects we learnt as kids. For most of us, this signifies a point of no return, a stage when we are already lawyers,  engineers or doctors and there is no way to go back in time to make a drastic career change.

This social experience mirrors what was always believed to happen in nature. We start our life as a single cell embryo which divides to give rise to cells that are capable of forming the entire organism. These multi-potential cells are called stem cells (specifically embryonic stem cells as they are found in the embryo). But with each subsequent division, the new cells become highly specialized, committed to performing unique functions. Some of the cells mature into muscle cells, some become fat cells, and some turn into nerve cells and together make a functional organism, whether it is a mouse or a human being. 

One of the most interesting questions in Biology was, like many individuals in their career path, have these cells too reached a point of no return?  Can they no longer give rise to any other cell type except the kind they are committed to form? Or can the mature adult cells be reprogrammed to revert to their earlier uncommitted state?

This year’s Nobel Prize for Physiology or Medicine, honors two scientists who answered the latter question with a resounding “Yes, the adult human cells are indeed reprogrammable! “ Sir John B. Gurdon of U.K and Shinya Yamanaka of Japan have been awarded the 2012 prize for the discovery that mature cells can be reprogrammed to become pluripotent (cells capable of giving rise to many different kinds of cells).

Remember Dolly, the sheep, which made “cloning” a household word in the early 90’s?  She was created by a process of nuclear transfer where the nucleus of the cell, which contains the entire genetic information of the organism, was taken out of an adult sheep cell and placed inside an enucleated egg cell, to form an embryo.

John Gurdon performed such a nuclear transfer in 1962. For the first time he showed that the nucleus of a mature frog intestinal cell, when placed inside an egg cell which had its nucleus removed, could reprogram itself and regain its non- specialized nature. The reprogrammed cell divided like a regular embryo and successfully produced live tadpoles, paving the way for research that led to the creation of Dolly. This revolutionary experiment disproved the dogma that adult cells are irreversibly committed into specialized cell types. 

But nuclear transfer into enucleated egg cells is a difficult process.  It also raises ethical questions about using human egg cells and playing God by creating human embryos that have to be destroyed to obtain the stem cells from them. In a quest to find an alternate route to reprogram mature adult cells into pluripotent stem cells, Shinya Yamanaka resorted to a totally different approach. He identified genes that are responsible for the non- specialized nature of embryonic stem cells. He then expressed these genes in the mature adult cells. And viola! He could convert the mature committed cells into immature stem cells that had the potential to give rise to many different cell types. The creation of these cells, termed induced pluripotent stem cells (iPSCs), first published in 2006, marked a significant development in cellular biology.

Together, these two discoveries changed our understanding about development of cells and by extension, the whole organism. They opened up the tantalizing prospect of creating different cell types including skin and liver from adult cells. Imagine the possibility of regenerating any tissue that has been lost by accident or disease! The iPSCs created from diseased individuals would also be of great value in screening drugs for treatment.

Of course, more research has to be carried out into the safety and practicality of using these cells in humans for therapy and improved methods have to be devised for creating these cells. But today, let us celebrate two individuals who have been bestowed with one of the highest honors for their contributions to the advancement of science.

Taming the fat

Fat has become an obsession with me now. Having always been a rather "chubby kid" (which I keep telling people is because of stopping my dance lessons and not because of the chocolate bars that went into my stomach day after day for more than a decade) I hardly bothered about weighty issues before. But all that has changed in the last few years.

We live in a world where obesity and associated problems like heart disease and diabetes have reached epidemic proportions. Efforts to lose weight and stay fit have become worldwide obsessions. The fat bug has hit me too, but with a small difference. I desperately want my cells to start storing fat. And I get terribly depressed when the cells remain lean and refuse to become fat.

Of course, when I say “my cells” I don’t really mean the cells in my body, but the cells from mice that I am doing my experiments with.

So why am I so concerned with mouse cells becoming fat?

To make a long story relatively short, let me start from the beginning, of my research project and of life itself.

When an embryo forms, it starts as a single cell which then divides many times and gives rise to other cells that make up different tissues and organs. The cells formed at the early stage are guided by specific proteins inside them to develop into specialized cells capable of performing unique functions.

I am working with a protein X that has many functions. Mice which don’t have this protein have many problems, one of which is the inability to make fat cells. Thus we know that X is important to tell the cells that they have to become fat cells. But we don’t know how this message is conveyed to the cells. Thus started my quest to find out how X regulates the formation of the fat cells from their precursor cells.

Scientific research often involves losing something to gain something bigger. From being someone who follows a vegetarian lifestyle to avoid killing animals, I became ready to kill mouse embryos to take out pre-fat cells from them and study them in the lab. I grow these cells, try to activate or inhibit other proteins inside them and try to make them mature into fat cells even though they don’t have the protein X. This gives me clues about the communication network inside the cells through which X tells them to become fat cells.

As I unravel the mystery behind the development of fat cells in the mice, does it have any relevance to us human beings? After all who cares if the mice are fat or lean and why do I wait with so much excitement to see fat cells under the microscope?

Recently, it was identified that a family with a defective X protein suffers from lipodystrophy which is a condition charecterized by loss of fat. This tells me that my findings about the protein X regulating fat cell formation in mice would be applicable to humans too.

Only when we understand the basics of how cells get the signal to become fat cells, can we design drugs to interfere with these signals and thus prevent them from becoming fat cells.

So my research aims to take a small step in understanding fat cell development. But we still have a long way to go before we can use this knowledge to treat obesity. Till then, I will make sure that I keep away from those French fries and pastries and so should you too.

To know more about obesity and the troubles it causes, this is a good starting point.

Initiation

I like to think that I project an approachable and affable personality with an aura of friendliness (Yeah, I know that I think a bit too much about myself). Unfortunately, though people do come and talk to me, the comfortable conversations last only till I open my mouth and let it out that I am pursuing a doctoral degree in the field of molecular biology. Immediately the atmosphere changes and I can see a mix of awe, pity, fear and disinterest on the other person's face and the conversation goes downhill from there. I can totally relate to the other person's feelings as the same thing happens to me when I meet people who talk about fiscal deficit and hyperbolic discounting.

I think that the basic problem is that we are so intimidated by the jargon used by people in specialized fields, that we lose the interest to try and understand the huge body of research being done in pursuit of understanding how things work.

I would like to use this space to to illustrate that behind all the mysterious reagents, the shiny and not so shiny instrumentation and the seemingly complicated codes, lie simple truths about life that make a fascinating read.

Through this blog i hope to convince you that science is not all Greek and Latin unless of course you live in Greece or Rome.

Hope the journey is enjoyable and enlightening.