Ageing, cancer and the length of your chromosomes

In human cells, DNA is formed into chromosomes which have long sections of DNA at their ends, called telomeres. The main role of telomeres is to protect the ends of the chromosomes, just like plastic ends of shoelaces. Each time a cell divides, the telomeres shorten. Without them, the main part of the chromosome containing our life-giving genes would become shorter thus preventing our cells to function properly. Telomere shortening is known to be associated with cancer, ageing and loss of stem cell function.

The aim of the Tel Stem Cell project is to determine the role of telomere-length regulators (such as specific proteins and genes) in cancer, ageing and stem cell biology. For this purpose, normal mice are compared with "knockout" mice: genetically engineered mice that lack the particular gene, which the project studies.

In 2009, Professor Blasco’s team showed for the first time that a telomere-binding protein can suppress tumour formation and stop premature tissues ageing. A gene known as TRF1 commands the production of a telomere binding protein and whilst no one knew what this gene did, Professor Blasco’s group produced a knockout mouse, and proved that it ages quicker and is proner to develop cancer. A year later a similar function was shown for another telomere-binding protein, known as TPP1. While TPP1 was shown to have an essential role in telomere elongation by telomerase, another telomere-bound protein known as RAP1, was dispensable for telomere capping and had instead an important role in gene-expression by binding throughout chromosome arms.

The project will also study the effect of telomere-length regulators on stem cells behaviour. This will help identify the specific role played by stem cells in ageing and cancer. As the longest telomeres have been found in adult stem cells, new telomere length maps could be used to identify the location of the niches of adult stem cells.

Professor Maria A. Blasco is one of the leading experts in telomere science. She has received the EMBO Gold Medal and the Körber European Science Award amongst many other scientific prizes. She was appointed to the EMBO Council in 2008, has authored over 150 scientific papers and has made major contributions to the field of telomeres and telomerase.

Glossary

DNA (deoxyribonucleic acid) is the genetic material in all living organisms. It is a code to produce proteins. DNA is made up of two long chains of a sugar-phosphate backbone and four nucleic acid bases which pair up and keep the two complementary strands together. The four bases are A (adenine), T (thymine), G (guanine) and C (cytosine): A pairs with T and G pairs with C.
Regions of our DNA code for particular proteins. These regions are known as genes.

A chromosome is a structure of DNA wrapped around proteins, found in the nucleus of the cell.

A telomere is a repeating section of DNA: TTAGGG on one strand, and AATCCC on the other, found at the ends of chromosomes protecting them from damage.

An enzyme is a biological catalyst. Enzymes can change the rate of biochemical reactions (usually within living organisms), and are made of proteins.

Telomerase is the enzyme that adds TTAGGG sequences to the ends of the chromosomes thereby preventing any loss of the important DNA within the chromosome during cell division.

A knockout mouse is a mouse that has been genetically engineered to lack a particular gene. This allows researchers to study any differences between knockout and normal mice and therefore determine the roles of that particular gene.

Stem cells are cells that have not yet specialised into a particular cell type.