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Molecular Biology PhD Position Opportunity @ BSMS UK

Molecular Biology PhD Position Opportunity @ BSMS UK

Molecular Biology PhD Position Opportunity @ BSMS UK: Brighton and Sussex Medical School (BSMS) is an equal partnership between the Universities of Sussex and Brighton together with NHS organisations throughout the South East region. The arrangements for the school’s governance reflect this approach and students are awarded joint BM BS degrees of both universities. Molecular Biology PhD Position Opportunity @ BSMS UK

Molecular Biology PhD Position Opportunity @ BSMS UK

NOVEL ROLES FOR RIBONUCLEASES IN CELL PROFILERATION

Supervisors: Prof Sarah Newbury, Prof Simon Morley, Dr Chris Jones

Molecular Biology PhD Position Opportunity @ BSMS UK

Project Description: Regulation of cell proliferation is of crucial importance to all multicellular organisms. Cells must proliferate throughout development in order for the organism to grow from an egg to an adult. Proliferation must also occur to repair damaged areas during the process of wound healing. Control of proliferation is vitally important to allow individual animals and their constituent organs to grow to reach and not exceed their correct sizes, as well as to maintain symmetry between the left and right sides of an animal. Uncontrolled cell proliferation is a hallmark of cancer with many genes involved in growth and proliferation implicated in cancer progression.

Molecular Biology PhD Position Opportunity @ BSMS UK

Using fruit flies as a model organism, we have recently discovered that cell proliferation can be regulated by an enzyme named Dis3L2. This enzyme is known to destroy messenger RNA molecules (mRNAs) which instruct the cell to make particular proteins. By comparing mutant fruit flies lacking Dis3L2 with normal individuals, we have found that lack of Dis3L2 results in wings that are much larger than normal. The wings grow from larval wing imaginal discs, which are also much larger in the mutant. Our results are particularly interesting because mutations in the equivalent human gene, DIS3L2, result in Perlman syndrome and susceptibility to a kidney cancer called Wilms’ tumour. Perlman syndrome is an overgrowth condition where affected children display pre-natal gigantism and abnormal enlargement of organs (e.g. kidneys). Therefore mutations in Dis3L2 in both fruit flies and humans result in the overgrowth of cells within some organs, showing an excellent conservation of this biological pathway between these organisms and demonstrating the usefulness of fruit flies to understand this disease.

This project aims to understand the role of RNA stability in control of cell proliferation. The project will use a comprehensive state-of-the-art toolset of techniques (including RNA-seq, molecular biology, genetics, bioimaging techniques and bioinformatics) to identify the RNA targets of this ribonuclease as well as the cellular pathways involved. The model organism Drosophila will first be used to establish the regulatory mechanisms involved which will then be followed up by analysis of related pathways in human cells with proliferation or cancer-associated phenotypes. This project will provide valuable insights into a new cellular pathway which can be used in the development of new disease therapeutics.

Funding Notes: Applicants for this 3.5-year BSMS-funded PhD starting in October 2017 should possess or expect to be awarded a minimum of a First or Upper Second Class Honours degree (or equivalent) in Biochemistry, Molecular Genetics or a relevant biomedical related subject. This studentship is only open to UK and EU citizens. Informal enquiries should be directed to Prof. Sarah Newbury (s.newbury@bsms.ac.uk).
Applications should be submitted via University of Brighton application portal (view website). Please contact BSMS Research Degrees Administrator (researchdegrees@bsms.ac.uk) should you require any assistance.

References:

  • Towler BP, Jones CI, Harper KL, Waldron JA and Newbury, SF. (2016) A novel role for the 3′-5′ exoribonuclease Dis3L2 in controlling cell proliferation and tissue growth. RNA Biology 2016 Dec;13(12):1286-1299. DOI: 10.1080/15476286.2016.1232238
  • Jones, C.I., Pashler, A.L., Towler, B.P., Robinson, S.R, Newbury, S.F. (2016) RNA-seq reveals post-transcriptional regulation of Drosophila insulin-like peptide dilp8 and the neuropeptide-like precursor Nplp2 by the exoribonuclease Pacman/XRN1. Nucleic Acids Research. 44 (1): 267-280. (doi: 10.1093/nar/gkv1336)
  • Towler, B.P., Jones, C.I ., Viegas, S.C., Apura, P., Waldron, J.A., Smalley, S.K., Arraiano, C.M. and Newbury, S.F. (2015) The 3’-5’ exoribonuclease Dis3 regulates the expression of specific microRNAs in Drosophila wing imaginal discs. RNA Biology: 12(7):728-41. (doi: 10.1080/15476286.2015.1040978)
  • Waldron, J.A. Jones, C.I., Grima, D.P., Hebbes, S., Towler, B.P., Crossman, S.H., Zabolotskaya, M.V. and Newbury, S.F. (2015). The 5′-3′ exoribonuclease Pacman/Xrn1 affects apoptosis and regulates expression of the pro-apoptotic mRNAs hid and reaper. Biology Open 4(5):649-60. (doi: 10.1242/bio.201410199.)

Application deadline: Friday 9 June 2017

Molecular Biology PhD Position Opportunity @ BSMS UK

View Original Notification: https://www.bsms.ac.uk/postgraduate/research-degrees/phd-opportunities.aspx

 

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