Completed Genetics & Molecular Biology Cells, Biochemistry & Physiology

Analysis of regulation of telomerase action and telomere capping function by the telomeric complex.

In plain English

AI plain-English summary

Every time a cell divides, it must solve a problem at the very ends of its chromosomes—and this project will unpick the molecular machinery that keeps those ends from fraying or fusing. The problem is that chromosome ends look like broken DNA to a cell’s repair systems, which would mistakenly try to glue them together. Specialised caps called telomeres, built from repetitive DNA and maintained by the enzyme telomerase, prevent this. But telomerase must be precisely controlled: too little activity and telomeres shorten, triggering cell ageing; too much and they lengthen, a hallmark of many cancers. Researchers do not yet understand how the protein complex that coats telomeric DNA regulates telomerase’s action and simultaneously protects the chromosome end from being mistaken for damage. This is fundamental science. The work uses simple fungi as a model to dissect the regulatory mechanisms, with the long-term goal of applying that knowledge to human biology. If successful, it will reveal the molecular dials that tune telomerase activity—insight that could eventually inform strategies for cancer treatment (where telomerase is overactive) or regenerative medicine (where controlled telomere lengthening might delay cellular ageing). No immediate practical application is expected, but past fundamental discoveries about telomeres and telomerase earned a Nobel Prize and opened entire fields of biomedical research.

View original technical description
A cell‘s genome is organized into linear entities, the chromosomes. Because the ends of chromosomes pose unsolvable problems to the machinery that duplicates the rest of the chromosome and are subject to being easily degraded, specialized structures have evolved, the telomeres, to perform the replicative and protective functions. These structures are maintained by an enzyme, telomerase, that is responsible for replicating the DNA telomeres are made of. Telomere functions are performed by specific factors that are bound onto telomeric DNA. Among these functions is the regulation of the activity of telomerase itself, which is tuned so that telomeric DNA is neither lost beyond a certain level nor elongated beyond a certain threshold. The goal of my research will be to understand how this regulation of telomerase is achieved. In addition, I will also address how telomeres protect the ends of chromosomes from a host of cellular activities that deal with damaged DNA (chromsome ends in fact resembles damaged, or ‘broken‘, DNA). Because telomere function has consequences for human diseases, such as cancer, the ultimate goal will be to understand the biology of human telomeres, but this will be achieved by using simple unicellular fungi as model systems.

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Researchers

Alessandro Bianchi (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Identification of molecular link between telomeres and telomerase and investigation of the mechanism underlying telomerase recruitment and activation
Telomere Biology Lab
The role of DNA binding and nucleolytic activities within mammalian telomerase
Analysis of regulation of telomerase action and telomere capping function by the telomeric complex
Chromatin Structure and Telomere Uncapping

Original classification

Fellowship

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