The objective of this PhD project is to determine the extent to which presence of obstructive sleep apnoea in obese patients influences gene expression, epigenetic variation, systemic inflammation, adipose tissue characteristics and cardiometabolic risk factors. We will study the effect bariatric-surgery induced weight loss has on remission of OSA and the potential mechanistics of this effect. We will also study variation in the gut microbiome withbariatric surgery. We will prioritise possible mechanistics by which bariatric surgery improves OSA and cardiovascular risk and metabolic derangements using network based analyses.
Obesity has become a global public heath challenge affecting almost half a billion adults. Vascular disease is a common feature amongst the obese population. The effects of obesity on inflammation and HDL dysfunction are more marked when complicated by OSA. HDL antioxidant function both in vitro and in vivo are more compromised and adipose tissue inflammation is enhanced when obesity is complicated with OSA. HDL is known to have an anti-inflammatory effect in adipose tissue. Epigenetics is an emerging area of huge potential to uncover novel molecular mechanisms underlying many diseases. It is not clear to what extent OSA affects gene expression.
Whilst bariatric surgery dramatically reduces weight, improves adipose tissue characteristics, improves OSA, cardiovascular and metabolic risk profiles in obese patients and reduces overall mortality but the mechanisms that underlie many of these favourable changes remain unclear.
Our aim is to study investigate the mechanistics of OSA induced cardiometabolic and adipose tissue changes. We will study the impact of OSA on gene expression, epigenetic modifications, including DNA methylation and microRNAs,, various aspects of HDL functionality, lipoproteins metabolism and LDL quality. We will also begin to explore the way in which the gut microbiome is altered following bariatic surgery and how this relates to OSA and other cardiovascular endpoints.
The successful candidate will gain extensive experience in genetic, cardiovascular science and lipidology, as well as basic training in aspects of biochemistry and molecular biology analysis. The project is therefore suited to an individual keen to engage in cardiovascular genetics research. Upon completion, progression into a postdoctoral career within academia or industry would be anticipated.
Applicants should hold, or expect to obtain, a degree (or equivalent) in biochemistry, molecular biology, genetics or a related area. An appropriate Masters or other post-graduate degrees and previous experience of in general and/or a molecular laboratory, and enrichment techniques would be beneficial but are not essential.
This 3-year PhD project is open to UK/EU and non-EU nationals but no funding is provided. Applicants must therefore be able to evidence their ability to provide self-arranged funding. The anticipated start date is July 2016, but this is flexible. Annual tuition fees for this project are currently:
*UK/EU nationals: £14,000
Non-EU nationals: £26,500
There is potential to commence the study in January 2016 if this suits the successful candidate.
Please direct applications in the following format to Dr Handrean Soran: [email protected]
• Academic CV
• Official academic transcripts
• Contact details for two suitable referees
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date.
• Evidence of funding.
Any enquiries relating to the project and/or suitability should be directed to Dr Soran.
Reza Aghamohammadzadeh, Adam S. Greenstein, Rahul Yadav, Maria Jeziorska, Salam Hama, Fardad Soltani, Phil W. Pemberton, Richard Unwin, Basil Ammori, Handrean Soran, Anthony M. Heagerty. The Effects of Weight-Reducing Surgery on Human Small Artery Function: Evidence for Reduction in Adipocyte Inflammation, and the Restoration of Normal Perivascular Anticontractile Activity Despite Persistent Obesity. JACC 2013; 62: 128-35.
High Density Lipoprotein Antioxidant Function is Impaired and Adipose Tissue Inflammation is More Pronounced in Obese Patients with Increasing Severity of Obstructive Sleep Apnea. Rahl Yadav, Michael France, Reza Aghamohammadzadeh, Akheel A. Syed, Rayaz Malik, Adam Greenstein, Paul Durrington, Martin Gibson, Basil Ammori, Maria Jeziorska, Handrean Soran. J Clin Endocrinol Metab. 2014 May 13:jc20133939. Epub ahead of print.
Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, Laing I, Yates AP, Pemberton PW, Malik RA, Heagerty AM. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation. 2009; 119: 1661-70.
Greenstein AS, Paranthaman R, Burns A, Jackson A, Malik RA, Baldwin RC, Heagerty AM. Cerebrovascular damage in late-life depression is associated with structural and functional abnormalities of subcutaneous small arteries. Hypertension. 2010 Oct; 56: 734-40.
Rakyan VK1, Down TA, Balding DJ, Beck S. Epigenome-wide association studies for common human diseases. Nat Rev Genet. 2011 Jul 12; 12: 529-41.
Ng JW, Barrett LM, Wong A, Kuh D, Smith GD, Relton CL. The role of longitudinal cohort studies in epigenetic epidemiology: challenges and opportunities. Genome Biol. 2012 doi: 10.1186/gb-2012-13-6-246.