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Linking androgen excess and metabolic dysfunction using a machine liver perfusion model


Institute of Metabolism and Systems Research

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Prof W Arlt , Dr S Afford , Dr Lina Schiffer No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

BACKGROUND: Polycystic ovary syndrome (PCOS) affects 10% of women. In PCOS androgen excess drives subfertility and an adverse metabolic profile with an increased risk for the development of insulin resistance, type 2 diabetes mellitus, obesity and non-alcoholic fatty liver disease.

PROJECT: This PhD project in Prof Arlt’s multi-disciplinary research group will investigate how local androgen activation affects the global metabolic profile of the liver with the overall aim to identify novel therapeutic targets to control androgen excess and metabolic complications. Together with the Birmingham Machine Perfusion Research Group led by Dr Simon Afford, this collaborative project will develop the use of normothermic machine liver perfusion (NMLP) – a novel technique for the functional recovery of marginal liver transplants – as a tool to study liver metabolism including the activation and inactivation of steroids by liver enzymes.

ENVIRONMENT: This PhD project is embedded in the on-going inter-disciplinary PCOS research program led by Prof Arlt (DAISy-PCOS, Dissecting Androgen Excess and Metabolic Dysfunction in PCOS), which comprises several ex-vivo projects, multi-centre clinical phenotyping and intervention studies and computational approaches. Additionally, the research team is developing a public and patient engagement campaign to educate about PCOS. As part of this PhD project, funding is available for in-depth public engagement training.

TECHNIQUES IN THIS PROJECT: targeted and untargeted metabolomics; liquid chromatography-tandem mass spectrometry; normothermic machine liver perfusion; molecular biology; steroid biochemistry; transcriptomics.

Applications are invited for a 3-year fully-funded PhD Studentship starting from October 2020.

Person Specification
Applicants should have a relevant background and strong interest in human biology, clinical chemistry and metabolism and its application to human health and disease. Previous experience in a research lab environment is essential. Experience with the following techniques is desirable: tandem mass spectrometry, tissue culture, standard molecular biology techniques such as qPCR. Applicants should be enthusiastic, self-motivated, and excellent team players. Due to the collaborative and inter-disciplinary nature of the project, outstanding communication skills and the ability and enjoyment of analytical, translational and creative thinking are required. Applicants should hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant biological or chemistry degree.

How to apply

Informal enquiries are encouraged and should be directed to Prof Wiebke Arlt ([Email Address Removed]) or Dr Lina Schiffer ([Email Address Removed])

To be considered for this studentship, please send the following documents to Dr Lina Schiffer ([Email Address Removed]):
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.


References

AKR1C3-Mediated Adipose Androgen Generation Drives Lipotoxicity in Women With Polycystic Ovary Syndrome. O'Reilly MW, Kempegowda P, Walsh M, Taylor AE, Manolopoulos KN, Allwood JW, Semple RK, Hebenstreit D, Dunn WB, Tomlinson JW, Arlt W. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3327-3339. doi: 10.1210/jc.2017-00947. PMID: 28645211

11-Oxygenated C19 Steroids Are the Predominant Androgens in Polycystic Ovary Syndrome. O'Reilly MW, Kempegowda P, Jenkinson C, Taylor AE, Quanson JL, Storbeck KH, Arlt W. J Clin Endocrinol Metab. 2017 Mar 1;102(3):840-848. doi: 10.1210/jc.2016-3285. PMID: 27901631

Transplantation of discarded livers following viability testing with normothermic machine perfusion. Mergental H, Laing RW, Kirkham AJ, Perera MTPR, Boteon YL, Attard J, Barton D, Curbishley S, Wilkhu M, Neil DAH, Hübscher SG, Muiesan P, Isaac JR, Roberts KJ, Abradelo M, Schlegel A, Ferguson J, Cilliers H, Bion J, Adams DH, Morris C, Friend PJ, Yap C, Afford SC, Mirza DF. Nat Commun. 2020 Jun 16;11(1):2939. doi: 10.1038/s41467-020-16251-3. PMID: 32546694


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