School of Life Sciences

Bianchi Lab

Our laboratory studies telomeres, which are nucleoprotein structures found at the ends of Eukaryotic chromosomes.

We are interested in telomeres because they carry out important functions in cells. These functions are so relevant to cellular physiology and to the preservation of the genome that telomeres were postulated to exist in the 1930s, based on genetic observations, well before they were physically observed and characterized. 

Today we know that telomeres are composed of arrays of short double-stranded DNA repeats terminating in single-stranded overhangs at the chromosome terminus, which serve as binding substrates for a large number of proteins that constitute the telomeric complex.

The DNA repeats are maintained by a specialized reverse transcriptase enzyme, telomerase, which uses an RNA template for their synthesis.

When telomerase is absent, as is the case in most human somatic tissues, the telomeres shorten with each cell division because DNA polymerases cannot fully replicate them. Thus, the length of the repeat arrays determines the number of divisions that a cell can go through, and therefore telomeres dictate the proliferative potential of a cell. A lot of recent research has implicated telomere shortening in affecting aging and also in functioning as a barrier against tumor suppression, by limiting the ability of cancer cells to divide indefinitely.

On the other hand, when telomeres become dysfunctional (for example by becoming too short) they can be an important cause of genome instability, particularly if the mechanisms that guard against insults to the genome are dismantled. Under these circumstances loss of the telomeres leads to end-to-end fusions of chromosomes and this gives rise to repeated cycles of breakage and fusions when cells divide. The end result is that genes can be lost or amplified in the precess, and both of these events can cause tumor formation.

Despite our growing understanding of telomeres, a number of fascinating questions remain to be addressed which are central both to our curiosity of how a cell works and to the fight against human disease. We are trying to contribute to this understanding thanks to funding by the MRC and CRUK.

                                                                 

Contact

Dr Alessandro Bianchi

Senior Lecturer

University of Sussex

Genome Damage and Stability Centre
Brighton, BN1 9RQ

E a.bianchi@sussex.ac.uk

T +44 1273 872 673

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