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(BBSRC DTP) Cardiac Physiology in the World’s Oldest Vertebrate, The Greenland Shark


Faculty of Biology, Medicine and Health

About the Project

The life span of the Greenland shark is at least 272 years and may be as long as 500 years making this animal the longest living vertebrate on the planet1. It was one of the lesser-known species of sharks up until 2016 when its extreme longevity was revealed. The finding that they live in the deep, dark Arctic waters for hundreds of years has captured the imagination of the world and the attention of scientists. How does an animal born in Shakespeare’s time still patrol the deep today? This extreme longevity is particularly interesting with respect to the heart, because heart disease is synonymous with aging in humans. What structures do their hearts have that permit this extreme longevity? Does the heart underlie the ability of this shark to live so long?

This PhD will explore the cardiac phenotype of the Greenland shark by investigating hallmarks of human cardiac aging2 in the shark using tissue collected from sharks whose age spans 50 to 280 years of age (+/100 years). The investigation has a 3-pronged approach. (1) The student will assess DNA methylation patterns in the shark heart tissue to understand its association with age3,4. (2) The student will investigate mitochondrial function using biochemical assays and electron microscopy tomography (nano-level 3D EM) to investigate subcellular morphology associated with long life (mitochondria and caveolae)5. (3) The student will assess the regenerative capabilities of the shark heart using immunohistochemistry and molecular assays.

Upon completion the student will have employed cross cutting investigative methods (‘omics/DNA-methylation patterns and 3D nano-EM tomography) combined with more conventional approaches of enzyme activity, and protein and gene expression analysis, to map the progression of age in the heart of the longest living vertebrate on the planet.

http://shiels.lab.manchester.ac.uk/
https://www.research.manchester.ac.uk/portal/gina.galli.html
https://www.research.manchester.ac.uk/portal/en/researchers/holly-shiels(d9ec86ad-8c25-4033-9322-ccb8358a0a1e)/publications.html
https://www.research.manchester.ac.uk/portal/adam.stevens.html
https://www.manchester.ac.uk/research/mhs/christian.pinali/

Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website http://www.manchester.ac.uk/bbsrcdtpstudentships

Funding Notes

Funding will cover UK tuition fees/stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website View Website

References

[1] Nielsen J, Hedeholm RB, Heinemeier J, Bushnell PG, Christiansen JS, Olsen J, Ramsey CB, Brill RW, Simon M, Steffensen KF, Steffensen JF. Eye lens radiocarbon reveals centuries of longevity in the Greenland shark (Somniosus microcephalus). Science. 2016 Aug 12;353(6300):702-4.

[2] López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013 Jun 6;153(6):1194-217.

[3] Peat JR, Ortega-Recalde O, Kardailsky O, Hore TA. The elephant shark methylome reveals conservation of epigenetic regulation across jawed vertebrates. F1000Research. 2017;6.

[4] Lowe R, Barton C, Jenkins CA, Ernst C, Forman O, Fernandez-Twinn DS, Bock C, Rossiter SJ, Faulkes CG, Ozanne SE, Walter L. Ageing-associated DNA methylation dynamics are a molecular readout of lifespan variation among mammalian species. Genome biology. 2018 Dec;19(1):22.

[5] Fridolfsson HN, Kawaraguchi Y, Ali SS, Panneerselvam M, Niesman IR, Finley JC, Kellerhals SE, Migita MY, Okada H, Moreno AL, Jennings M. Mitochondria-localized caveolin in adaptation to cellular stress and injury. The FASEB Journal. 2012 Nov;26(11):4637-49.

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