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From pond life to Nobel Prize: the story of telomeres and their role in disease

ESC Congress News 2015 - London

Presenters at a Young Investigators Award session yesterday were inspired by the presence of Nobel Prize laureate Elizabeth Blackburn. She was awarded the 2009 Nobel Prize in Physiology or Medicine for discovering the molecular nature of telomeres (the ends of eukaryotic chromosomes that serve as protective caps) and the enzyme telomerase. ‘Telomeres are intertwined with cardiovascular disease,’ Blackburn told ESC Congress News - short telomere length with CVD mortality, CVD risk factors and cardiomyopathy.

Cardiovascular Disease in the Elderly
Cardiac Cellular Biology


However, while long telomeres are undoubtedly good for CVD risk, they don’t seem to be uniformly good in cancer, ‘since they give cells permission to go on multiplying,’ explained Blackburn, from the University of California, San Francisco.

Telomere length also appears to interact with a range of other factors. One observational study in patients with bladder cancer showed that those with both short telomeres and high levels of depression had higher risks of mortality than those with either short telomeres or high levels of depression alone. ‘So in future the name of the game will be precision medicine, where we integrate different information to see how it comes together for each individual,’ she predicted.

Elizabeth Blackburn at Saturday’s Inaugural Session. She advised young investigators to focus on their work ‘for concentrated patches’.It was as a post doc in Joe Gall’s lab at Yale that Blackburn was introduced to Tetrahymena, a ciliated protozoan which eventually lay the foundations for her work in telomeres. ‘Tetrahymena are literally pond scum and have thousands of tiny, short, linear chromosomes that are readily accessible,’ she explained. She decided to focus on what happened at the ends of these mini chromosomes, and found that telomeres consisted of a repetitive sequence of six DNA units (TTAGGG), which could vary from 20 units in some Tetrahymena, up to 70 in others.

She hypothesised that the new telomeres were not copied from existing DNA, but were created de novo during cell division through enzymatic action. With her PhD student Carol Greider (with whom she shared the Nobel Prize, together with Jack Szostak), Blackburn broke open the Tetrahymena cells and was able to visualise the enzyme’s action on gels. They established that this novel enzyme activity was not an artefact and named it telomerase.

Blackburn’s advice to young investigators is to focus ‘for concentrated patches’ on their work. ‘While you can take time off for part of the year there are periods when you need to engross yourself totally in the science, because such complete immersion facilitates thinking,’ she said.

Although successful scientists need to be able to persist, there is a real skill in knowing when to let go. With such challenges peer group support is vitally important: ‘Usually your family won’t have any idea what you’re trying to achieve. You need advice from other people in your lab, institution and wider research field who understand what you are going after.’