Rarely has a Nobel award received such media buzz as that of Elizabeth Blackburn, Jack Szostak and Carol Greider. If cracking the DNA code revealed the ‘secret of life’, Blackburn’s discovery of telomerase was heralded as the ‘fountain of youth’.
The truth, while not quite so magical, is impressive enough. Telomerase is the enzyme that makes telomere DNA – protective ‘caps’ that allow DNA strands to split without damage during cell division as bodies grow.
Scientists had long suspected the existence of these caps but it was while studying the single-celled Tetrahymena (‘pond-scum’) that Blackburn discovered that the DNA sequence CCCCAA was repeated several times at the ends of the chromosomes.
When Blackburn presented her results in 1980, Szostak suggested they try an experiment by grafting the CCCCAA sequence to previously vulnerable minichromosomes in yeast. Sure enough, the telomere protected them from degradation. As the two organisms were not related, this showed a fundamental mechanism common to most plants and animals.
Szostak discovered some yeast cells had mutations that caused a shortening of the telomeres. These cells aged rapidly and soon failed.
Blackburn’s team set out to explore whether telomere DNA was created by an unknown enzyme. On Christmas Day, 1984, graduate student Carol Greider observed activity in a cell extract. Greider and Blackburn found that the enzyme, which they called telomerase, contained an RNA blueprint of the CCCCAA sequence and proteins, allowing telomerase to build longer telomeres. Blackburn then showed that telomere shortening in Tetrahymena could be caused by mutating telomerase itself.
In humans, telomerase is a two-edged sword. From more recent research, Blackburn now believes that telomere shortening in normal cells of the body can hasten some of the most common diseases of aging. If short telomeres accelerate this aspect of the ageing process, long telomeres seem to slow it down. Future work may attempt to stimulate telomere elongation in diseased cells, such as in anaemia. However, despite media speculation, preventing telomere shortening will not make Methuselahs of us.
Conversely, telomerase is often overly active in malignant cancer cells. Therefore, work is under way to explore the effect of targeting telomerase in those cancer cells that have already become malignant.
Elizabeth Helen Blackburn was born in November 1948 in Hobart, Tasmania. One of seven children born to two family physicians, she was encouraged to participate in science from an early age. She completed her BSc (1970) and MSc (1972) in biology at the University of Melbourne, her PhD (1975) from the University of Cambridge in England and did postdoctoral work at Yale in the US before joining the faculty at the University of California, Berkeley in 1978.
In 1990 she joined the Department of Microbiology and Immunology at UC San Francisco, where she served as Department Chair from 1993-99 and is now the Morris Herzstein Professor of Biology and Physiology in the Department of Biochemistry and Biophysics. She is also a Non-Resident Fellow of the Salk Institute.
In 2001 President Bush appointed her to the Council on Bioethics, but she was dismissed in 2004 in what is generally believed to be a political move because of her vocal support for human stem cell research.
Elsewhere, Blackburn has been widely honoured as (among others) President of the American Society for Cell Biology 1998 and of the American Association for Cancer Research in 2010. She has been elected a Foreign Fellow of the USA National Academy of Sciences and a Fellow of the American Academy of Arts and Sciences, the Royal Society of London, the American Academy of Microbiology and the American Association for the Advancement of Science.
In 2007 she was named one of TIME Magazine’s 100 Most Influential People and in 2010 was made a Companion of the Order of Australia. She is married to John Sedat, and has a son, Benjamin.
By Volker Steger
“Lots of caff eine for me please!”
But she is so alert already. The sketch comes out detailed, colourful and
humourous. There are even emoticons and sound eff ects (!).
So, this is the kind of professor I would have liked to have had.
„Bitte jede Menge Koff ein für mich!“
Dabei ist sie absolut wach. Es entsteht eine detaillierte, farbenfrohe und
witzige Zeichnung. Es gibt sogar Emoticons und Soundeff ekte (!).
Also, so eine Professorin hätte ich auch gerne gehabt.
Revealing the Mystery Ending
by Adam Smith
“It was a speed drawing exercise as I recall,” says Elizabeth Blackburn, and her rapidly sketched solution is a cyclical diagram. As far back as the 1930s, people had noticed that the tips of chromosomes seemed to serve a protective function, but what these telomeres, or end parts were, nobody knew. So the question facing Blackburn was how could you get at the ends of chromosomes, these hugely long threads of DNA depicted by the tangled blue mass at the top left of the picture. Given that the vast majority of chromosomal DNA is not at the ends, how on earth could you deal with the problem: “Aarrgghh!”
The solution that she and her co-Laureate Jack Szostak came up with lay in a tiny organism called tetrahymena. That’s the hairy little thing depicted swimming around in a pond full of waterlillies. Apart from its aesthetic appeal, this harmless creature contains lots of very, very small chromosomes, as shown by the row of parallel lines with little blobs at the end of them. And these short chromosomes of course have a relatively greater number of ends than the long chromosomes you normally find, giving you lots more ends to analyse.
What their analysis revealed is shown in the expanded telomere seen on the right; a very simple, repeated DNA sequence that extended all the way to the end of the chromosome. Next Blackburn and Szostak asked what would happen if they shortened the telomeric DNA in tetrahymena by an experimental trick. They observed that as the telomeres ran down, the organisms became sick, hence the sad yellow face.
They then reasoned that if the length of telomeres needed to be maintained for normal health, then hypothetically there might be an enzyme able to maintain them. So together with her graduate student Carol Grieder, who shared in the Nobel Prize (and this was the first time that any Nobel Prize in the sciences was awarded to more than one woman), Blackburn went looking for the enzyme in tetrahymena again. They found an enzyme, telomerase, that could add back the telomeric DNA that had been lost. Hence the now contented smiley face; “Aahhh” … Happiness.
What was true for one organism turned out to be true for all organisms. So tetrahymena takes us back to an understanding of the long chromosomes we see in most organisms, including humans.