The objective of this PhD project is to study the effect bariatric-surgery induced weight loss has on a gene expression, DNA methylation and lipidomics to determine master regulators of obesity associated metabolic derangements.
Obesity has become a global public heath challenge affecting almost half a billion adults and an estimated 40 million children. Vascular disease is a common feature amongst the obese population, and is manifest clinically as myocardial infarction, stroke and hypertension.
Obesity is associated with increased cardiovascular morbidity and mortality. The most certain method of achieving significant and sustained weight reduction is by weight-reducing surgery and this is the only established method of reducing obesity-associated morbidity and mortality. However, whilst bariatric surgery dramatically improves adipose tissue characteristics, perivascular adipose tissue function, cardiovascular and metabolic risk profiles in obese patients and reduces overall mortality the mechanisms that underlie these metabolic and cardiovascular improvements remain unclear.
Samples will be taken from peripheral blood, adipose tissue and visceral fat, before, during and post-operatively and used to study DNA methylation, microRNAs and gene expression, together with several aspects of HDL functionality and lipidomics. Utilising systems biology /network analyses we will prioritise pathways and loci of key mechanistic importance.
The successful candidate will gain extensive experience in genetics, cardiovascular science and lipidology as well as basic training in aspects of biochemistry and molecular 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 Handrean 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.