Dr C Henriques, Prof I Bellantuono
No more applications being accepted
Self-Funded PhD Students Only
About the Project
As we age, we develop chronic diseases, which diminish our quality of life. Because the number of people over the age of 65 is set to double over the next 50 years, we urgently need to develop effective therapies to improve health in the aged.
A major medical problem of ageing is that the different tissues in our bodies become damaged over time. A major reason behind this is that the tips of our chromosomes, called telomeres become damaged with ageing. Telomeres are a protective “cap” that, similarly to the tips of shoelaces, “hold” our DNA together. However, telomeres shorten with ageing causing cells to die or become “lazy”, what we call senescent.
Senescent cells accumulate abnormally with ageing and cause disease. In a young body, the immune system clears away senescent cells, whereas with ageing this does not seem to work efficiently, and we do not know why. It is likely that, as we age, our immune system becomes defective in its ability to clear senescent cells from tissues – if we could understand this, we might be able to put it right.
This PhD project will identify the key reasons behind this and test a strategy to promote the clearance of senescent cells in aged, damaged tissues.
We will particularly focus on the gut, since this is one of the first tissues to suffer in ageing and has the potential to influence health in many other tissues, using zebrafish as a model organism.
We will ask the key questions:
1-Can we heal the ends of our chromosomes and boost the immune system? Will this be sufficient to get rid of senescent cells in old animals? We will do this by sophisticated genetic manipulation of zebrafish.
2- Can some of the already available medicine help? We will do this by performing a targeted drug test in old zebrafish.
The ultimate aim of this work, part of a larger research programme on-going in the lab, is to discover new ways to stimulate our natural immune system to clear senescent cells, reducing inflammation and tissue damage, which are major contributors to the increased disease incidence with ageing and consequent decreased quality of life in old age.
Funding Notes
This project is open for self-funded students.
Eligibility Requirements:
Candidates should have research experience, ideally from a lab placement where the student had the opportunity to work on a project, from which they can provide references for. Ideally, candidates should have experience in working with the following: adult zebrafish, immuno-staining, molecular biology (DNA extraction and PCRs), histology, FACS and fluorescence microscopy imaging and analysis.
References
1 Lujambio, A. To clear, or not to clear (senescent cells)? That is the question. Bioessays 38 Suppl 1, S56-64, doi:10.1002/bies.201670910 (2016).
2 Carneiro, M. C. et al. Short Telomeres in Key Tissues Initiate Local and Systemic Aging in Zebrafish. PLoS genetics 12, e1005798, doi:10.1371/journal.pgen.1005798 (2016).
3 Henriques, C. M., Carneiro, M. C., Tenente, I. M., Jacinto, A. & Ferreira, M. G. Telomerase is required for zebrafish lifespan. PLoS genetics 9, e1003214, doi:10.1371/journal.pgen.1003214 (2013).
4 Brown, D. M. & Goljanek-Whysall, K. microRNAs: Modulators of the underlying pathophysiology of sarcopenia? Ageing Res Rev, doi:10.1016/j.arr.2015.08.007 (2015).
5 Misra, J. et al. Zoledronate Attenuates Accumulation of DNA Damage in Mesenchymal Stem Cells and Protects Their Function. Stem Cells 34, 756-767, doi:10.1002/stem.2255 (2016).
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