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Chromatin regulation by carbon dioxide


Department of Biosciences

Prof M Cann , Prof S Rocha Friday, January 22, 2021 Competition Funded PhD Project (Students Worldwide)
Durham United Kingdom Biochemistry Cell Biology Molecular Biology

About the Project

Carbon dioxide is a constituent of all known biological systems yet its molecular interactions with the cell are unexplored. Cells are exposed to fluctuating carbon dioxide through altered environmental conditions, changes in cell metabolism, and the effects of lifestyle and pathology. This proposal will illuminate the cell biology of this crucial yet relatively under explored molecule of central importance to all life on Earth.

The project will use newly developed tools in proteomics and mass spectrometry to trap carbon dioxide on mammalian proteins. Carbamylation is an important post-translational modification for altering protein function through the reversible alteration of amino acid side chain functionality. Specifically, the project will investigate how the carbamate PTM influences chromatin function and transcriptional activity. The project will provide the first comprehensive analyses of the influence of protein carbamylation on chromatin and provide key insight into how cells adapt in response to elevated carbon dioxide.

This is a multi-disciplinary Ph.D. that will provide training in cell biology, mass spectrometry, analytical techniques of physical chemistry, proteomics and bioinformatics. No prior training in these areas is required. Training in these diverse disciplines will be provided in the laboratories of the project supervisors at both Durham and Liverpool Universities. The successful student will complete the Ph.D. with a broad interdisciplinary skill set valuable to both academia and industry.

Informal enquiries may be made to

HOW TO APPLY

Applications should be made by emailing with a CV and a covering letter, including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project/s and at the selected University. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

 

In addition to the CV and covering letter, please email a completed copy of the NLD BBSRC DTP Studentship Application Details Form (Word document) to , noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and 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.

References

(2018) The identification of carbon dioxide mediated protein post-translational modifications. Nature Communications 9:3092 | DOI: 10.1038/s41467-018-05475-z.
(2018) The intracellular immune receptor Rx1 regulates the DNA-binding activity of a Golden2-like transcription factor. Journal of Biological Chemistry, 293, 3218-33.
(2015) The potato NLR immune receptor Rx1 is a pathogen dependent DNA deforming protein. Journal of Biological Chemistry, 290, 24945-60.
(2012) Elevated Carbon Dioxide Blunts Mammalian cAMP Signaling Dependent on Inositol 1,4,5-Triphosphate Receptor-mediated Ca2+ Release. Journal of Biological Chemistry, 287, 26291-301.
(2019) Hypoxia induces rapid changes to histone methylation and reprograms chromatin. Science. 363, 1222-1226.
(2018) SINHCAF/FAM60A and SIN3A specifically repress HIF 2alpha expression. Biochem. J. 475, 2073-2090.
(2016) VHL inhibitor VH298 is a potent and selective chemical probe of hypoxic signalling downstream of HIFalpha hydroxylation. Nature Comms. 7, 13312.
(2015) HIF-1alpha restricts NF-kappaB-dependent gene expression to control innate immunity signals. Dis. Models and Mech. 8, 169-181.
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