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EASTBIO: Why do the effects of calorie restriction differ between males and females?

  • Full or part time
    Dr Sharon Mitchell
    Dr W Cawthorn
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Supervisors:

Dr Sharon Mitchell (University of Aberdeen)
https://www.abdn.ac.uk/energetics-research/

Dr William Cawthorn (University of Edinburgh)
https://www.research.ed.ac.uk/portal/en/persons/will-cawthorn(51332b93-94ef-47a7-a092-004cbc21fddc).html

Calorie restriction (CR) delays the ageing process, reduces the risk of age-related disease such as cancer and cardiovascular disease, and extends lifespan in several species. While recent studies recognise some of these benefits in humans, the mechanisms behind the CR response remain elusive. Many effects of CR represent adaptations selected for during evolution to confer a survival advantage during periods of food scarcity. Thus, elucidating the mechanisms behind the CR response may reveal fundamental insights about human biology.

Based on the observation that the level of restriction is positively related to longevity in rodents, the primary supervisor (Dr Sharon Mitchell) has fully characterised the response to graded CR (0, 10, 20, 30 & 40% fewer calories than individual baseline intake) in male C57BL/6 mice (1). Alongside this work, research from the lab of the second supervisor, Dr William Cawthorn, has revealed striking sex differences in the effects of 30% CR. Specifically, Dr Cawthorn’s research reveals that 30% CR decreases fat mass and improves glucose tolerance in male mice, but that female mice resist these effects ((2) and unpublished). These sex differences in glucose homeostasis appear to reflect differential glucose uptake in adipose tissue, including bone marrow adipose. In addition, the Cawthorn lab has found sex differences in the immunological responses, with CR decreasing circulating monocytes and increasing T-cells in males but not in females (unpublished data). These findings echo the sex differences in metabolic homeostasis that have been observed in humans (3). However, the mechanistic basis for these fundamental sex differences remains to be determined.

This PhD studentship will address this gap in knowledge by defining the female response to graded CR. This will build on the dataset gathered in males, which was based on a BBSRC-funded grant (BB/G009953/1). All animal work will be carried out in the Aberdeen facility with the opportunity for the successful student to apply for their HO personal licence. The student will be trained in a number of in vivo animal procedures, including body composition analysis by dual x-ray absorptiometry and resting metabolic rate. Further techniques will include transcriptomic analysis of white adipose tissue, flow cytometry to assess circulating leukocytes, and micro-computed tomography to determine bone architecture and bone marrow adiposity. Much of the laboratory-based work will be carried out at the Edinburgh site with students analysing the bone and immunological phenotypes. Through these studies, the student will also gain valuable analytical skills, including large-scale transcriptomic and imaging datasets.

Application Procedure:
http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts and CV to Alison McLeod at . Two references should be provided by the deadline using the EASTBIO reference form. Please advise your referees to return the reference form to .

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership. This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body. Queries on eligibility? Email Alison McLeod ().

Candidates should have (or expect to achieve) a minimum of a First Class Honours degree in a relevant subject. Applicants with a minimum of a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.

References

1. S. E. Mitchell, et al., Oncotarget 6, (2015).
2. W. P. Cawthorn, et al., Endocrinology 157, (2016).
3. F. Mauvais-Jarvis, Physiol Behav (2017).



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