Our research aims to answer fundamental questions about how cells and organisms work at the molecular and biochemical level. We study the structures and properties of DNA, RNA and protein molecules, and how these molecules interact within cells to form complex functional networks. We are also working towards applications of our knowledge to address important real-world problems.
Self-funded PhD opportunities
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.
- 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
- Olorunniji, F.J. Rosser, S.J. and Stark, W.M. (2016) Site-specific recombinases: molecular machines for the Genetic Revolution. Biochem. J. 473, 673-684.
- Olorunniji, F.J. et al. (2017). Control of serine integrase recombination directionality by fusion with the directionality factor . Nucleic Acids Res. 45, 8635-8645.
- Proudfoot, C., McPherson, A.L., Kolb, A.F. and Stark, W.M. (2011) Zinc Finger recombinases with adaptable DNA sequence specificity. PLoS ONE 6, e19537.
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.
- yeast genetics
- molecular biology
- mammalian cell culture and cell biology
- high resolution imaging/confocal microscopy
- 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.”
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.
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.
- 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.
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 , 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:
- The effects of SUMOylation on EPAC1 activity, subcellular localisation and interaction with regulatory proteins
- Determine the role of EPAC1 SUMOylation on the regulation of cytokine signalling in vascular endothelial cells
- cell culture
- light microscopy
- confocal microscopy
- reporter genes
- western blotting
- 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.
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 molecular and biochemical approaches including structural analysis at the atomic level by X-ray crystallography, NMR spectrometry, and other biophysical methods. The knowledge gained by this research gives us opportunity to invent and develop novel ways of altering biological processes to our advantage, with applications in molecular medicine, biotechnology, synthetic biology, as well as industry.
- Duration: 3/4 years full-time; 5 years part-time
PhD programmes in biochemistry and biotechnology will carry out a cutting-edge research project in an area that aligns with the expertise of one or more of our principal investigators in the fields of biochemistry and biotechnology. The subject of the project may be fundamental “blue skies” science or may be targeted at an important application. Projects may also be related to basic science and integrate with our existing research themes, while other projects are more focused on translational aspects of our research.
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 and X-ray crystallography
- 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
Our PhD programme provides excellent training in cutting edge technologies that will be applicable to career prospects in both academia and industry. Many of our graduates become postdoctoral research associates while others go on to take up positions within industry, either locally or overseas. We have strong academic connections with many international collaborators in universities and research institutes.
Funds are available through the College of Medical, Veterinary and Life Sciences to allow visits to international laboratories where part of your project can be carried out. This provides an excellent opportunity for networking and increasing your scientific knowledge and skill set.
Awarded or expected First-class or high Upper Second-class BSc degree.
English Language requirements for applicants whose first language is not English.
Fees and funding
- £4,327 UK/EU
- £21,020 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:
- Re-submission by a research student £500
- Submission for a higher degree by published work £1,250
- Submission of thesis after deadline lapsed £320
- 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
Depending on the nature of the research project, some students will be expected to pay a bench fee (also known as research support costs) to cover additional costs. The exact amount will be provided in the offer letter.
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 for EU students
The UK government has confirmed that EU nationals will remain eligible to apply for Research Council PhD studentships at UK institutions for 2019/20 to help cover costs for the duration of their study.
- £4,260 UK/EU
- £20,150 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 £480
- Submission for a higher degree by published work £1,200
- Submission of thesis after deadline lapsed £300
- 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) £270
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.
- BBSRC Doctoral Training Partnerships
- External funding information
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 overarching 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
How to apply
Identify potential supervisors
All Postgraduate Research Students are allocated a supervisor who will act 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. Please note, even if you have spoken to an academic staff member about your proposal you still need to submit an online application form.
You can find relevant academic staff members with our staff research interests search.
Gather your documents
Before applying please make sure you gather the following supporting documentation:
- Final or current degree transcripts including grades (and an official translation, if needed) – scanned copy in colour of the original document
- Degree certificates (and an official translation, if needed): scanned copy in colour of the original document
- Two references on headed paper (academic and/or professional).
- Research proposal, CV, samples of written work as per requirements for each subject area.
To complete your application we will need two references (one must be academic the other can be academic or professional).
There are two options for you to submit references as part of your application. You can upload a document as part of your application or you can enter in your referee’s contact details and we will contact them to request a reference.
Option 1 – Uploading as part of the application form
Your references should be on official headed paper. These should also be signed by the referee. You can then upload these via theOnline Application form with the rest your documents to complete the application process.
Please be aware that documents must not exceed 5MB in size and therefore you may have to upload your documents separately. The online system allow you to upload supporting documents only in PDF format. For a free PDF writer go to www.pdfforge.org.
Option 2 - Entering contact details as part of the application form
If you enter your referees contact details including email on the application form we will email them requesting they submit a reference once you have submitted the application form. When the referee responds and sends a reference you will be sent an email to confirm the university has received this.
After submitting your application form
Use our Applicant Self Service uploading documents function to submit a new reference. We can also accept confidential references direct to email@example.com, from the referee’s university or business email account.
Once you have all your supporting documentation you can apply through our Online Application System
I've applied. What next?
If you have any other trouble accessing Applicant Self-Service, please see Application Troubleshooting/FAQs.
If you are requested to upload further documents
Log into the Applicant Self Service and scroll down to the Admissions Section. The screenshot below indicates the section on the page, and the specific area you should go to, highlighted in red:
Documents must be uploaded in .jpg, .jpeg or .pdf format and must not exceed 5MB in size. There is a maximum 10MB upload size for all documents with the application.
Once a decision has been made regarding your application the Research Admissions Office will contact you by email.
If you are made an unconditional offer
You can accept your offer through the Applicant-Self-Service by clicking on the ‘Accept/Decline link’ for your chosen programme under the ‘Admissions Section’ at the bottom of the Applicant Self Service screen. You can access the Applicant Self Service by using the link, username and password you used to apply and selecting the “Self Service” button below your application.
Please make sure you accept your unconditional offer within 4 weeks of receiving your offer. If you are an international student your CAS will not be issued until you have accepted an unconditional offer.
If you are made a conditional offer
If you accept a conditional offer then the offer status on Applicant-Self-Service will change to ‘incomplete’ to indicate that the application is incomplete until such time as all the conditions are met.
Your offer letter will list all the conditions that apply to your offer and you can upload the required document(s) through Applicant Self Service. If you have met the conditions satisfactorily, you will automatically be sent an unconditional offer.
If your application is unsuccessful
If your application is unsuccessful then we will send you an email to inform you of this which will outline the reason why we have been unable to offer you a place on this particular programme. Please note that your application status will be updated to 'Cancelled' on Applicant Self Service if the offer is rejected.
Deferring your offer
If you want to defer your start date, please contact us directly at firstname.lastname@example.org. We need authorisation from your supervisor before we confirm your request to defer. Once we have this we will contact you by email to confirm.
How to register
After you have accepted an unconditional offer you will receive an email nearer to the start of your studies to tell you how to register online using the University's MyCampus website, the University’s student information system. That email will provide you with your personal login details and the website address. Please ensure that your email address is kept up to date as all correspondence is sent via email. You can update your email address through the Applicant Self Service Portal under the Personal Information section.
- If you have any questions about your application before you apply: contact our College of Medical, Veterinary and Life Sciences Graduate School
- If you have any questions after you have submitted your application: contact our Admissions team
- Any references may be submitted by email to: email@example.com
- Advice on visa, immigrations and the Academic Technology Approval Scheme (ATAS) can be found on our International student pages