Wednesday, October 10, 2012

The 2012 Nobel Prize in Chemistry

Today the 2012 Nobel Prize in Chemistry was awarded to Robert Lefkowitz and Brian Kobilka for their work on G protein-coupled receptors.

How do signals from outside the cell get transmitted into the cell? It's a question that long plagued scientists and the answer underlies many if not all vital cellular processes. It was thought that there were protein receptors on the surface of the cell that recognized molecules and in the process of this recognition, specific events were triggered inside the cell - the action of the hormone adrenaline, for example. In the 1960's Lefkowitz's lab used radioactive hormones to isolate the receptor responsible for the action of adrenaline - the B2 adrenergic receptor. This initial step of isolating the receptor was key in allowing scientists to characterize the biochemical properties of the protein. Isolation of the protein in an active form was not trivial since the receptor had portions outside the cell, portions in the membrane of the cell, and portions inside the cell - it is a transmembrane protein.

In the 1980's Kobilka joined Lefkowitz's lab and set out trying to isolate the gene encoding the B2 adreneric receptor. He was successful and when they analyzed the gene sequence, they realized there were other similar genes - thereby implicating a gene family. As it turns out, there are many genes that encode these protein receptors, all similar in function, but differing in what external signal they recognize and transmit inside the cell. - smell, light, histamine (think allergies), mood, appetite and sleep (serotonin).

Kobilka left Lefkowitz's lab and established his own research group studying these receptors - especially trying to determine their molecular structure. In the last couple of years, his group succeeded in solving the structure of the B2 adrenergic receptor just as a hormone has bound giving new intricate details on how these important signal is transmitted to the cell.

It is suggested that more than half of all drugs act on this family of G protein-coupled receptors highlighting the importance of understanding exactly how these proteins function and opening doors for the treatment of many disorders.

Monday, October 08, 2012

The 2012 Nobel Prize in Physiology or Medicine

The Nobel Committee announced the awarding of the 2012 Nobel Prize in Physiology or Medicine to Sir John B. Gurdon and Shinya Yamanaka for their work on the reprogramming of mature cells to immature pluripotent cells.

It is rather amazing to think that the variety of different cells within our bodies start from a single cell. Those early cells that have the ability to turn into many different types of cells are called pluripotent stem cells. The cellular differentiation process is relatively well understood. But, is it possible for a mature cell to revert to its immature, pluripotent state, or is cellular differentiation a one-way street?

Fifty years ago Sir John Gurdon performed an experiment to test this idea. He replaced the nucleus of a frog egg with the nucleus of a mature cell from a tadpole intestine. This egg developed into a normal adult frog. After subsequent repetition of the experiment it became clear that the information for cellular differentiation still resided within the mature cell. In fact, cells do have the ability to go backward.

After this discovery, the question became, how does this happen? What are the keys to the underlying mechanism of differentiation? In the early 21st century, Shinya Yamanaka took genes thought to play a role in keeping cells in an immature state and injected them into mature cells in varying combinations looking for combinations that would turn those mature cells into immature cells. He and his colleagues did find a combination that reprogrammed these mature cells and surprisingly, it took only 4 genes to accomplish this remarkable task. They went on to show that these reprogrammed cells could differentiate into many different cell types.

The implications of this work are profound. Gurdon's original observation led to the cloning of mammals - Dolly the Sheep being the first success. The ability to reprogram cells by the introduction of just a few specific genes creates cellular tools that allow us to get a better understanding of the underlying processes, the study of changes in healthy versus diseased cells, and even the potential to use these findings to treat degenerative diseases.

There are many unanswered questions about the potential of these reprogrammed stem cells. Dolly the Sheep only lived 6 years and these genetically reprogrammed stem cells appear to have a propensity to form tumors. However, the two discoveries awarded this year's prize have opened up amazing possibilities.