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Getting the cat out of the bag: advancing the genetic knowledge in feline and human type 2 diabetes.

This project is no longer listed in the FindAPhD
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  • Full or part time
    Dr Forcada
    Dr Niessen
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Supervisors: Dr Yaiza Forcada, Professor Mark Walker (Institute of Cellular Medicine (Diabetes), Newcastle University) Dr. Stijn Niessen, Professor Brian Catchpole

Department: Clinical Science and Services

Feline and human type 2 diabetes mellitus (T2DM) share many commonalities, including clinical presentation, pancreatic pathology and response to treatment. Recent work at the RVC for the first time ever also documented shared genetic factors. A polymorphism in the melanocortin-4-receptor gene was associated with a higher risk of T2DM in overweight domestic short hair cats. Subsequently, a world-first cat Genome Wide Association Study of feline T2D was performed by the applicants using DNA of 900 cats identifying a number of significant SNPs associated with feline T2DM. Several of these SNPs have previously been associated with human T2DM, though others have not. Those latter SNPs are especially interesting, providing possible novel information on the pathophysiology of the disease in both species, hence also hinting towards possible novel therapeutic targets.

The aim of this project will be to teach a PhD-student in all aspects of molecular biology by researching the genetic background of feline and human T2DM.

Specific objectives will include:

Evaluation of the most promising SNPs identified during the feline GWAS, which have previously been associated with human T2DM, to then
- Perform feline candidate gene approach studies to confirm/deny their relevance;
- Perform functional studies using feline and human cell culture (predominantly beta-cells, striated muscle and liver) through transfection with and without SNP affected vectors.
Evaluation of the most promising SNPs identified during the feline GWAS, which have NOT previously been associated with human T2DM, to then:
- Perform feline and human candidate gene approach studies to confirm/deny their relevance;
- Perform functional studies using feline and human cell culture (as above) through transfection with and without SNP affected vectors
The studentship will commence in October 2016.

Interviews for studentships - will be held on 16th March or in the w/c 21st March 2016 at the RVC’s Camden or Hawkshead Campuses
http://www.rvc.ac.uk/study/postgraduate/phd

Funding Notes

This is a three year fully funded studentship, supported by Boehringer Ingelheim. It is open to Home/EU applicants only. International students are welcome to apply but must be able to pay the difference between UK/EU and international tuition fees.

References

Forcada Y, Holder A, Church DB, Catchpole B. A polymorphism in the melanocortin 4 receptor gene (MC4R:c.92C>T) is associated with diabetes mellitus in overweight domestic shorthaired cats. Vet Intern Med. 2014 Mar-Apr;28(2):458-64. doi: 10.1111/jvim.12275. Epub 2013 Dec 26.
Strawbridge RJ, Dupuis J, Prokopenko I, Barker A, Ahlqvist E, Rybin D, Petrie JR, Travers ME, Bouatia-Naji N, Dimas AS, Nica A, Wheeler E, Chen H, Voight BF, Taneera J, Kanoni S, Peden JF, Turrini F, Gustafsson S, Zabena C, Almgren P, Barker DJ, Barnes D, Dennison EM, Eriksson JG, Eriksson P, Eury E, Folkersen L, Fox CS, Frayling TM, Goel A, Gu HF, Horikoshi M, Isomaa B, Jackson AU, Jameson KA, Kajantie E, Kerr-Conte J, Kuulasmaa T, Kuusisto J, Loos RJ, Luan J, Makrilakis K, Manning AK, Martínez-Larrad MT, Narisu N, Nastase Mannila M, Ohrvik J, Osmond C, Pascoe L, Payne F, Sayer AA, Sennblad B, Silveira A, Stancáková A, Stirrups K, Swift AJ, Syvänen AC, Tuomi T, van 't Hooft FM, Walker M, Weedon MN, Xie W, Zethelius B; DIAGRAM Consortium; GIANT Consortium; MuTHER Consortium; CARDIoGRAM Consortium; C4D Consortium, Ongen H, Mälarstig A, Hopewell JC, Saleheen D, Chambers J, Parish S, Danesh J, Kooner J, Ostenson CG, Lind L, Cooper CC, Serrano-Ríos M, Ferrannini E, Forsen TJ, Clarke R, Franzosi MG, Seedorf U, Watkins H, Froguel P, Johnson P, Deloukas P, Collins FS, Laakso M, Dermitzakis ET, Boehnke M, McCarthy MI, Wareham NJ, Groop L, Pattou F, Gloyn AL, Dedoussis GV, Lyssenko V, Meigs JB, Barroso I, Watanabe RM, Ingelsson E, Langenberg C, Hamsten A, Florez JC. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. Diabetes. 2011 Oct;60(10):2624-34. doi: 10.2337/db11-0415. Epub 2011 Aug 26.
Xie W, Wood AR, Lyssenko V, Weedon MN, Knowles JW, Alkayyali S, Assimes TL, Quertermous T, Abbasi F, Paananen J, Häring H, Hansen T, Pedersen O, Smith U, Laakso M; MAGIC Investigators; DIAGRAM Consortium; GENESIS Consortium; RISC Consortium, Dekker JM, Nolan JJ, Groop L, Ferrannini E, Adam KP, Gall WE, Frayling TM, Walker M. Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes. Diabetes. 2013 Jun;62(6):2141-50. doi: 10.2337/db12-0876. Epub 2013 Feb 1.

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