One of the Nobel Prize winners, Professor Elizabeth Blackburn, happens to be on the editorial board of the Biology Image Library, the website I work on for my full-time job. Well done Elizabeth!
[Edit 3rd December 2010: Sadly, Our Green Earth no longer exists but the owner has very kindly handed back copyright of my articles to me. Here, for your reading pleasure, is The Most Important Scientific Discovery of 2009…]
The Most Important Scientific Discovery of 2009
Deoxyribose nucleic acid, or DNA, is a molecule that provides the code for life. This long polymer of four nitrogenous bases; adenine (A), cytosine (C), guanine (G) and thymine (T), along with its “backbone” of sugar and phosphate molecules, is found in almost every cell in the body in the form of 46 pairs of chromosomes. It gives the instructions for our cells to create the thousands of proteins that carry out specific functions in our bodies. Proteins control everything from the colour of our hair to the digestion of our food, and even tiny mistakes in the code can cause mayhem in the form of genetic diseases, cancers and mutations.
The Integrity of Life
Every cell in our body is ultimately generated from the division of one cell, the zygote; an egg cell fertilised by a sperm cell. As this cell grows and divides, the DNA that it contains; 23 chromosomes from our father and 23 from our mother, is copied exactly so that almost every cell in our body contains the same genetic information. Different cell types look different, perform different functions and produce different proteins due to a complex system of switching on the genes for proteins that are needed for that cell type, and switching off those that are not needed. Given that there are approximately 10 trillion cells in the average human body, and each cell is on average just 10 µm in diameter, it is remarkable to think that every single one of these tiny units contains up to 3 metres of the same DNA for the duration of our lifetime.
The Nobel Prize for Medicine or Physiology, 2009
The integrity and longevity of DNA has been attributed to regions on the ends of chromosomes called telomeres. Telomeres are long sequences of DNA that repeat a particular pattern of the four bases: CCCCAA. Repeats of this sequence, found on the ends of chromosomes, act as a “cap” and have been known for some time to stabilise the DNA molecules (1). However, three researchers – an Australian, Elizabeth Blackburn, American Carol Greider and British Jack Szostak – have recently been awarded the Nobel Prize for Medicine or Physiology for their collaborative research and discovery of a gene lying within the telomeres. This gene codes for a protein called telomerase.
Telomeres and Telomerase
Telomerase is a protein with a very special function. A minimum number of CCCCAA repetitions are needed to protect the coding regions of DNA within the chromosomes from degradation by enzymes (specialised proteins that catalyse chemical reactions). If the telomeres are broken down, this puts the main body of DNA – the part that codes for all the proteins that carry out our life functions – at risk of being degraded itself. Telomerase contains a short sequence of RNA, a similar molecule to DNA, which has the same sequence – CCCCAA (2). This acts as a template to repair and replenish the DNA repeats when they are broken down, and so this is how the stability of the molecule is maintained during cell growth and division (3). Without telomerase, our cells would lose repeats at a steady rate with each cell division until the coding DNA was eventually damaged (4). Animal cells have only a limited supply of this protein however, and so with the passing years, the ability of telomerase to protect our telomeres gradually decreases until the telomeres are completely degraded and the more important DNA begins to be eroded. This partially explains why we age and our cells eventually senesce, or die.
Implications for health and disease
This important discovery has many implications for further research. If we can understand how and why we age, this may lead us towards discovering more about diseases of ageing such as dementia and Parkinson’s, or cures for rare premature ageing diseases such as progeria. It may also help us to understand more about cancer, since a feature of many cancer types is that the production of telomerase is up regulated such that there is never a shortage of the protein. HeLa cells for example, a malignant cell line used commonly in cancer research, are considered to be “immortal” since propagation of these cells can occur indefinitely. The cells used in research today are exactly the same as those originally taken from the tumour of a woman called Henrietta Lacks who died from cancer in 1951. These and some other cancer cells produce enough telomerase that the telomeres do not shorten and the mutated DNA is preserved. By finding a way to down-regulate the telomerase gene in this case, it may be possible to develop treatments to halt or even reverse the proliferation of cancerous cells. Indeed, clinical trials are already underway to test a vaccine that targets cancer cells with high telomerase activity. A cure for cancer is a long way off yet, but thanks to these three researchers highly deserving of their Nobel Prize, we may just be one step closer.
- Greider, C.W. and Blackburn, E.H., Identification of a specific telomere terminal transferase activity in tetrahymena extracts, Cell 43: 405-413, 1985
- Press release of the Nobel Assembly at Karolinska Instituet, 10th October 2009, http://nobelprize.org/nobel_prizes/medicine/laureates/2009/press.pdf
- Wang, X., Kam, Z., Carlton, P.M., Xu, L., Sedat, J.W., Blackburn, E.H., Rapid telomere motions in live human cells analyzed by highly time-resolved microscopy, Epigenetics and Chromatin 1: 4, 2008
- Yu, G.-L., Bradley, J.D., Attardi, L.D., Blackburn, E.H., In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs, Nature 344 (6262) pp. 126-132