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Postgraduate research opportunities 

Biochemistry and Molecular Biology

Biochemistry

Our research aims to answer fundamental questions about how cells and organisms work at the molecular level. We study the structures and properties of DNA, RNA and protein molecules, and how these molecules interact within cells to form complex functional systems. We are also working towards applications of our knowledge to address important real-world problems.

PhD Research Projects

Mechanisms and applications of DNA site-specific recombinases

Outline & aim

Site-specific recombinases are enzymes that promote rearrangements of DNA molecules, by cutting and rejoining DNA strands at precise places within short target sequences (sites). For example, a specific piece of DNA can be cut out of a larger molecule, or its orientation can be reversed. Our research group aims to understand in detail how recombinases catalyse these reactions, and how they are controlled. To do this we use high-resolution structural data and advanced techniques for laboratory analysis. Site-specific recombinases have tremendous potential as tools for manipulating DNA in the fields of biotechnology, synthetic biology, and gene therapy. We are investigating how to engineer “designer recombinases” that are suitable for these purposes, and how to use them for novel applications.

The aim of the research project will be to advance our understanding in one of the areas outlined above. For example, the project might be an investigation of the mechanism of DNA strand cutting and rejoining, using novel “single-molecule” methodologies; or, to develop novel designer recombinases suitable for targeting specific genes in a living organism for deletion or modification.

Techniques

Analysis of high-resolution structures; protein expression, purification and biochemistry; methods for manipulation of DNA in E. coli; cloning, sequencing, sequence analysis; synthetic Biology; novel methods for gene assembly; advanced methods for analysis of protein-DNA complexes, including single-molecule methods

References

  • Olorunniji, F.J. and Stark, W.M. (2010) Catalysis of site-specific recombination by Tn3 resolvase. Biochem. Soc. Trans. 38, 417-421.
  • Prorocic, M.M., Wenlong, D., Olorunniji, F.J., Akopian, A., Schloetel, J.-G., Hannigan, A., McPherson, A.L. and Stark, W.M. (2012) Zinc-finger recombinase activities in vitro. Nucleic Acids Res. 39, 9316-9328.
  • Mouw, K.W., Rowland, S.J., Gajjar, M.M., Boocock, M.R., Stark, W.M. and Rice, P.A. (2008) Architecture of a serine recombinase-DNA regulatory complex. Mol. Cell 30, 145-155.

Contact

Marshall.Stark@glasgow.ac.uk

Defining the mechanism of abscission

Outline & aim

ESCRT proteins mediate membrane scission events involved in the down-regulation of ubiquitin-labelled receptors via the multivesicular body (MVB) pathway and in HIV budding from host cells. In addition, ESCRT proteins play a role in abscission, the final stage of cytokinesis. The ESCRT machinery is composed of four complexes: ESCRT-0, -I, -II and -III; and the modular composition of the ESCRT machinery is reflected in its various functions. At a precise time during cytokinesis, the ESCRT-I protein TSG101 and ESCRT-associated protein ALIX are recruited to the midbody through interactions with CEP55; TSG101 and ALIX in turn recruit ESCRT-III components. Thereafter, by a mechanism still not completely understood, ESCRT-III redistributes to the putative abscission sites, microtubules are severed and the daughter cells separate. However, the mechanisms by which this selective and specific redistribution of ESCRT proteins is regulated in space and time remain largely unsolved.

ESCRT components are phosphoproteins, so we reasoned that kinases and phosphatases are likely candidates for ESCRT regulation. We hypothesised that polo and aurora kinases and Cdc14 phosphatase may be potential regulators of ESCRT function due to their significant roles in controlling cytokinesis. This aspect of mitotic regulation of

ESCRT function will be investigated in this project, as we have shown that these kinases and phosphatases play a role; our challenge now is to define that role and to determine whether similar mechanisms operate in mammalian cells. This interface between signalling and trafficking is an important and active research theme worldwide, and you will join an active and collaborative group well versed in all the training aspects required for successful completion of a PhD.

The aim of the project is to define the role of aurora kinase, polo-like kinase and Cdc14 on ESCRT function in yeast and mammalian cells.

Techniques

Yeast genetics; molecular biology; mammalian cell culture and cell biology; high resolution imaging/confocal microscopy

References

  • M.S.Bhutta, B.Roy, G.W.Gould and C.J.McInerny Public Library of Science 1. (2014) In press. “Control of cytokinesis by polo and aurora kinases and Cdc14 phosphatase regulation of ESCRT proteins.”
  • H.Neto, A.Kaupisch, L.L.Collins and G.W.Gould. Molecular Biology of the Cell (2013) 24, 3633-3674. “Syntaxin 16 is required for early stages in cytokinesis.”

Contact

gwyn.gould@glasgow.ac.ukchris.mcinerny@glasgow.ac.uk

Protein folding and secretion in mammalian cells

Outline & aim

The ability of cells to correctly fold and assemble proteins is the final stage in protein synthesis. Protein folding requires a subset of proteins able to either catalyse folding reactions or act as molecular chaperones preventing non-productive protein aggregation. The inability of cells to carry out the folding process results in some of the most catastrophic mammalian diseases such as cystic fibrosis, Alzheimer's and CJD.

Techniques

We aim to understand how cells fold and assemble proteins we are studying this process in mammalian cells using a combination of cell biological and biochemical techniques.

References

  • Tavender, T.J., Springate, J.S., and Bulleid, N.J. (2010) Recycling of peroxiredoxin IV provides a novel pathway for disulphide formation in the endoplasmic reticulum. The EMBO J., 29, 4185-4197.
  • Braakman I. and Bulleid N.J. (2011) Protein folding and modification in the mammalian endoplasmic reticulum. Annual Reviews in Biochemistry, 80: 71–99.
  • Oka O.B., Pringle, M.A., Schopp, I.M., Braakman, I., Bulleid, N.J. (2013) ERdj5 Is the ER Reductase that Catalyzes the Removal of Non-Native Disulfides and Correct Folding of the LDL Receptor. Mol Cell., 50(6):793-804.

Contact

Neil.Bulleid@glasgow.ac.uk

The role of EPAC1 in the control of cytokine signalling in vascular endothelial cells

Outline & aims

We and others [1-3] have found that the cyclic AMP-activated signalling protein EPAC1 (exchange protein activated by cyclic AMP 1) promotes protective functions in vascular endothelial cells (VECs), including promotion of endothelial barrier function and induction of protein suppressors of cytokine signalling (eg SOCS3), and therefore plays a vital role in maintaining the health of the vasculature.

It is now clear that interactions with cellular binding proteins determine both the intracellular location and enzyme activity of EPAC1. For example, the cytoskeleton-associated, MAP1a-LC2 protein [4], recruits EPAC1 to microtubules and enhances its activity, whereas the nuclear-localised SUMO ligase, RanBP2 [5,6], suppresses EPAC1 activity at the nuclear pore complex.

Our aim now is to fully understand these control mechanisms with the long term goal of devising new therapies based on modulating protein interactions with EPAC1. Central to this goal is the new observation that EPAC1 becomes SUMOylated within the regulatory cyclic nucleotide binding domain (CNBD). Since the CNBD is responsible for direct activation by cyclic AMP and is also responsible for cytoskeletal recruitment through MAP1a-LC2, then SUMOylation represents a powerful new control mechanism for controlling EPAC1 localisation and activity.The student will therefore determine:

  1. The effects of SUMOylation on EPAC1 activity, subcellular localisation and interaction with regulatory proteins
  2. Determine the role of EPAC1 SUMOylation on the regulation of cytokine signalling in vascular endothelial cells

Techniques

Cell culture; light microscopy; confocal microscopy; immunofluorescence; reporter genes; western blotting

References

  • Sands, W.A., Woolson, H.D., Milne, G.R., Rutherford, C. and Palmer, T.M. (2006). Exchange protein activated by cyclic AMP (Epac)-mediated induction of suppressor of cytokine signaling 3 (SOCS-3) in vascular endothelial cells. Mol Cell Biol 26, 6333-46.
  • Yarwood, S.J., Borland, G., Sands, W.A. and Palmer, T.M. (2008). Identification of CCAAT/enhancer-binding proteins as exchange protein activated by cAMP-activated transcription factors that mediate the induction of the SOCS-3 gene. J Biol Chem. 283, 6843-53.
  • Borland, G., Smith, B.O. and Yarwood, S.J. (2009). EPAC proteins transduce diverse cellular actions of cAMP. Br J Pharmacol 6, 6.
  • Gupta, M. and Yarwood, S.J. (2005). MAP1A light chain 2 interacts with exchange protein activated by cyclic AMP 1 (EPAC1) to enhance Rap1 GTPase activity and cell adhesion. J Biol Chem 280, 8109-16.
  • Gloerich, M., Vliem, M.J., Prummel, E., Meijer, L.A., Rensen, M.G., Rehmann, H. and Bos, J.L. (2011). The nucleoporin RanBP2 tethers the cAMP effector Epac1 and inhibits its catalytic activity. J Cell Biol 193, 1009-20.
  • Liu, C., Takahashi, M., Li, Y., Dillon, T.J., Kaech, S. and Stork, P.J. (2010). The interaction of Epac1 and Ran promotes Rap1 activation at the nuclear envelope. Mol 30, 3956-69.

Contact

Stephen.Yarwood@glasgow.ac.uk

Overview

Our Biochemists and Molecular Biologists study the “molecules of life”, the essential molecular components of all living organisms. We aim to understand how these molecules perform their functions, using a variety of modern approaches including structural analysis at the atomic level by X-ray crystallography, NMR spectrometry, and biophysical methods, functional analysis of proteins and nucleic acids in vitro, molecular/systems analysis in living cells, and molecular genetics. Our knowledge gained by this research gives us opportunity to invent and develop novel ways of altering biological systems to our advantage, with applications in molecular medicine, biotechnology, and synthetic biology.

Study options

Postgraduate students aiming for a PhD will carry out a cutting-edge research project over 3-4 years in an area that aligns with the expertise of one or more of our Principal Investigators in the fields of Biochemistry and Molecular Biology. The subject of the project may be fundamental “blue skies” science or may be targeted at an important application. Some of our current research areas are:

  • Cell signalling mechanisms in mammals, plants and insects
  • Mitochondrial biogenesis and mitochondrial proteins
  • Mechanisms of DNA sequence rearrangements
  • DNA sequences in human disease
  • Genetic circuits and switches for synthetic biology
  • Plant molecular biology
  • Photosynthesis, plant photobiology, circadian factors in plants
  • Structural determination by NMR
  • Structural bioinformatics, molecular modelling
  • Drug receptors, molecular pharmacology
  • Nuclear genomic architecture
  • Mechanisms of intracellular trafficking
  • Protein folding, targeting and modification
  • Protein-protein and protein-DNA interactions
  • Cell-surface interactions

Supervisors

All our postgraduate research students are allocated a supervisor who acts as the main source of academic support and research mentoring.

You may want to identify a potential supervisor and contact them to discuss your research proposal before you apply.

Entry requirements

Awarded or expected 1st class or high upper 2nd class BSc degree.

English Language requirements for applicants whose first language is not English.

Fees and funding

Fees

2016/17

  • £4,121 UK/EU
  • £18,900 outside EU

Prices are based on the annual fee for full-time study. Fees for part-time study are half the full-time fee.

Additional fees for all students:

  • Submission by a research student £440
  • Submission for a higher degree by published work £890
  • Submission of thesis after deadline lapsed £140
  • Submission by staff in receipt of staff scholarship £680
  • Research students registered as non-supervised Thesis Pending students (50% refund will be granted if the student completes thesis within the first six months of the period) £250
  • General Council fee £50
  • Depending on the nature of the research project, some students will be expected to pay a bench fee to cover additional costs. The exact amount will be provided in the offer letter.

2017/18

  • £4,195 UK/EU*
  • £19,500 outside EU

Prices are based on the annual fee for full-time study. Fees for part-time study are half the full-time fee.

* We expect that tuition fees for EU students entering in 2017 will continue to be set at the same level as that for UK students.  However, future funding arrangements for EU students will be determined as part of the UK’s discussions on its future relationship.  If you are thinking of applying for 2017 entry, we would encourage you to do so in the usual way. For further information, please see the Research Councils UK statement on international collaboration and Universities UK Brexit FAQs for universities and students.

Additional fees for all students:

  • Fee for re-submission by a research student: £460
  • Submission for a higher degree by published work: £1,050
  • Submission of thesis after deadline lapsed: £250
  • Submission by staff in receipt of staff scholarship: £730
  • Research students registered as non-supervised Thesis Pending students (50% refund will be granted if the student completes thesis within the first six months of the period): £300
  • Registration/exam only fee: £150
  • General Council fee: £50

Alumni discount

A 10% discount is available to University of Glasgow alumni. This includes graduates and those who have completed a Junior Year Abroad, Exchange programme or International Summer School at the University of Glasgow. The discount is applied at registration for students who are not in receipt of another discount or scholarship funded by the University. No additional application is required.

 

Funding

Support

The College of Medical, Veterinary and Life Sciences Graduate School provides a vibrant, supportive and stimulating environment for all our postgraduate students. We aim to provide excellent support for our postgraduates through dedicated postgraduate convenors, highly trained supervisors and pastoral support for each student.
 
Our over-arching aim is to provide a research training environment that includes:

  • provision of excellent facilities and cutting edge techniques
  • training in essential research and generic skills
  • excellence in supervision and mentoring
  • interactive discussion groups and seminars
  • an atmosphere that fosters critical cultural policy and research analysis
  • synergy between research groups and areas
  • extensive multidisciplinary and collaborative research
  • extensive external collaborations both within and beyond the UK 
  • a robust generic skills programme including opportunities in social and commercial training
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