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The Molecular Basis Of The Sex-linked Functional Differences In B Cells

Reference	BB/W010747/1
Principal Investigator / Supervisor	Dr Sara Buonomo
Co-Investigators / Co-Supervisors	Dr Christopher Lucas, Professor Matthias Trost
Institution	University of Edinburgh
Department	Sch of Biological Sciences
Funding type	Research
Value (£)	104,857
Status	Completed
Type	Research Grant
Start date	01/08/2021
End date	31/01/2023
Duration	18 months

Abstract

unavailable

Summary

The risk of mortality from Covid-19 is up to two-fold higher in men versus women, especially in the middle-age category, across different cultures and social structures. However, the biological reasons behind this difference is unknown. Recent research has highlighted significant divergences in the immune system response between the two sexes. This observation has been paralleled by the discovery of tissue-specific euchromatinisation of the inactive X chromosome in both B and T cells, accompanied by the identification of immune-related genes that specifically escape X inactivation in B cells. One of these escapees, TLR7, is a receptor for ssRNA viruses such as SARSCoV- 2. Its increased dosage caused by bi-allelic expression in women, has been shown to be advantageous for B cells response upon stimulation of TLR7. Moreover, recent studies have shown hypomorphic alleles of TLR7 lead to severe Covid-19 in young men. We hypothesised that, following escape from X inactivation, double-dosage of one or more X-encoded genes involved in B cell activation could be at the basis of the sex-linked differential mortality from Covid-19. To identify the X-encoded B-cell specific proteins that are present in higher dosage in women, we propose an unbiased approach, employing quantitative mass spectrometry from B cells from healthy, middle-aged men and women. We thus aim at identifying relevant proteins which could represent potential pharmaceutical targets to improve the prognosis of SARS-CoV-2.

Committee	Not funded via Committee
Research Topics	Immunology
Research Priority	X – Research Priority information not available
Research Initiative	Covid19 Rapid Response [2020]
Funding Scheme	X – not Funded via a specific Funding Scheme

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