Postgraduate research 

Biochemistry & Biotechnology PhD/iPhD/MSc (Research)

Biochemistry

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.

  • PhD: 3-4 years full-time; 5 years part-time;
  • MSc (Research): 1 year full-time; 2 years part-time;

Research projects

Self-funded PhD opportunities

+++

Ubiquitin signals in Parkinson’s disease

Outline

Ubiquitin signalling controls almost every cellular process in humans, including targeting poorly folded proteins for destruction to prevent them harming the cell. When ubiquitin signalling goes wrong, many different disease states can occur, including neurodegenerative disorders such as Parkinsons Disease (PD).

One gene associated with PD is parkin, which gives rise to an enzyme responsible for tagging many different proteins with ubiquitin. The aims of this project are to understand on a biochemical and molecular level how parkin targets a specific substrate, Miro1, and how the ubiquitin signals applied to Miro1 are edited & interpreted.

This project will involve expressing and purifying multiprotein complexes, and developing protocols for generating the ubiquitin signals, and enzymatic assays for the regulation of these signals.

Techniques

  • Cloning and sequencing
  • Protein expression purification, and biochemistry
  • Assay development
  • X-ray crystallography
  • Cryo Electron Microscopy
  • Analysis of high resolution structures

Aims

Our overarching goal is to determine a previously hidden aspect of cells undergoing oxidative stress whereby their capacity to target proteins to mitochondria is substantially altered to benefit the cell (for example through control of mitochondrial Reactive Oxygen Species). The broader effects on function of resident mitochondrial transporters is also key to understand as a mechanism of stress-induced metabolic rewiring.

This will be achieved by three specific aims to be addressed in this project:

  1. To characterize new mitochondrial targeting mechanisms of proteins that become alternatively translated under oxidative stress
  2. To elucidate specific stress-induced modifications on the mitochondrial protein import components and inner membrane metabolite transporters that underpin their expanded transport capacity under stress
  3. To explore how misfolded and aggregated mitochondrial proteins are exported for clearance by the proteasome as a means to maintain a healthy protein balance within mitochondria and influence cell death pathways.

References

  1. Gundogdu M, Tadayon R, Salzano G, Shaw GS, Walden H. A mechanistic review of parkin activation. Biochim Biophys Acta Gen Subj. 2021 Jun;1865(6):129894. doi: 10.1016/j.bbagen.2021.129894.20.PMID: 33753174
  2. Kumar A, Chaugule VK, Condos TEC, Barber KR, Johnson C, Toth R, Sundaramoorthy R, Knebel A, Shaw GS, Walden H. Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity. Nat Struct Mol Biol. 2017 May;24(5):475-483. doi: 10.1038/nsmb.3400. Epub 2017 Apr 17.PMID: 28414322

Contact

Helen.walden@glasgow.ac.uk

---

+++

Mitochondria biogenesis and stress responses in health and disease

Outline

Maintenance of functional mitochondria is essential for life and an important therapeutic target in several diseases, including age-related neurodegenerative diseases. Mitochondrial dysfunction is linked to redox damage and dysregulation of mitochondrial protein homeostasis mechanisms. The burden of these to mitochondria can often lead to cell death. Mechanisms that control import of proteins and elimination of damaged proteins, redox regulation and protein homeostasis are therefore critical for safeguarding mitochondria under stress conditions and key to cell physiology. Despite their importance, these mechanisms remain elusive.

Our recent work has revealed that under stress conditions a number of proteins, many of them with critical antioxidant and chaperone functions, are targeted to mitochondria (particularly in the intermembrane space) via unconventional pathways. Once inside the mitochondria, these proteins protect the organelles from oxidative damage and protein aggregation, which pose a dual threat to cell homeostasis. It is critical to understand the key players and how they are imported to mitochondria to exert a pro-survival function, how they affect the function of critical proteins like the inner membrane metabolite transporters that are critical for metabolism and how they inhibit the onset of diseases like neurodegeneration.

Recent evidence from our lab has identified several proteins that undergo stress-dependent targeting to mitochondria where they either assist the physiological mitochondria biogenesis process or facilitate the elimination of damaged proteins by proteolytic systems like the proteasome. The project will therefore address how stress-responsive alterations of mitochondria biogenesis ensure mitochondria fitness and metabolic rewiring as a protection against irreversible damage.

Aims

Our overarching goal is to determine a previously hidden aspect of cells undergoing oxidative stress whereby their capacity to target proteins to mitochondria is substantially altered to benefit the cell (for example through control of mitochondrial Reactive Oxygen Species). The broader effects on function of resident mitochondrial transporters is also key to understand as a mechanism of stress-induced metabolic rewiring.

This will be achieved by three specific aims to be addressed in this project:

  1. To characterize new mitochondrial targeting mechanisms of proteins that become alternatively translated under oxidative stress
  2. To elucidate specific stress-induced modifications on the mitochondrial protein import components and inner membrane metabolite transporters that underpin their expanded transport capacity under stress
  3. To explore how misfolded and aggregated mitochondrial proteins are exported for clearance by the proteasome as a means to maintain a healthy protein balance within mitochondria and influence cell death pathways.

Training outcomes:

The student will be trained in several complementary biological disciplines in the laboratories of the supervisory team:

  1. Molecular biology and genetics approaches will be used to generate several yeast (S. cerevisiae) models for the project. Further, shRNA and CRISPR/Cas-9 approaches will be used for gene manipulations in mammalian cells (fibroblasts and cancer cell lines).
  2. Biochemistry and Cell Biology techniques will be employed to assess protein import, protein-protein interactions, intramitochondrial localization using FRET, split GFP and super-resolution microscopy and mitochondrial function using high-resolution respirometry
  3. Biophysical and structural biology assays will be applied for purified proteins in a reconstituted system using microscale thermophoresis and isothermal titration calorimetry for measuring binding affinities between proteins and NMR for structural analysis
  4. Bioinformatic and proteomics approaches will assist the student to elucidate unknown mitochondrial targeting motifs and identify redox-related PTMs on protein translocon components. Omics approaches will be performed in collaboration with experts (Redox modifications group at the National Proteome Facility, Beijing, China) and professional services. The student will learn to prepare the samples (including experimental design) for analysis as well as to analyse and interpret the results.
  5. Transferable skills (eg. communication, networking, time management) will be provided by the MVLS Researcher Development Plan and by tailor-made activities within the participating labs which are very active in KE activities (public engagement, Industry liaison events) and extended interactions with the EMBO, FEBS and international mitochondria research community.

References

  1. Kritsiligkou P et al (2017) Unconventional targeting of a thiol peroxidase to mitochondrial intermembrane space facilitates oxidative protein folding Cell Reports 18(11):2729-2741
  2. Banci L et al (2009) MIA40 is an oxidoreductase catalyzing oxidative protein folding in mitochondria, Nature Structural and Molecular Biology 16(2), 198-206
  3. Scialo, F. et al. (2016) Mitochondrial ROS Produced via Reverse Electron Transport Extend Animal Lifespan Cell Metab 23, 725-734
  4. Giampazolias et al (2017) Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency Nat Cell Biol. 2017 Sep;19:1116-1129

Contact

Kostas.tokatlidis@glasgow.ac.uk

---

+++

Exploring the structure and function of protein complexes by high-resolution cryo-EM

Outline & aim

Highly specialised protein complexes are critical regulators of cell division and homeostasis. The full understanding of the functional mechanisms of such complexes requires an in-depth knowledge of their structural organisation, which we study primarily by high resolution cryo-electron microscopy (cryo-EM) and single particle analysis. By resolving protein complexes in different functional states, representing snapshots of the complex in action, we aim at gaining detailed knowledge of their functional and regulatory mechanisms.

We also aim at obtaining information to guide on how to specifically target those complexes for therapeutic use. The structural data obtained is combined with further biochemical and biophysical information for a full functional characterisation.

Techniques

Our work focuses on high-resolution cryo-EM and single particle analysis, together with protein purification and biochemical/biophysical characterisation.

References

  1. Kišonaitė, M., Afanasyev, P., Tafilaku, J., Toste Rêgo, A., da Fonseca, P.C.A. (2021) “New insights into the human 26S proteasome function and regulation”, deposited online ahead of publication, bioRxiv preprint doi: 10.1101/2021.10.03.462214
  2. Morris, E.P. and da Fonseca, P.C.A. (2021) “How to Build a Proteasome”, Nat. Struct. Mol. Biol. 28: 409–410.
  3. Toste Rêgo, A. and da Fonseca, P.C.A. (2019) “Cryo-EM analysis of fully recombinant human 20S and 20S PA200 proteasome complexes”, Mol. Cell, 76: 138-147.
  4. Morris, E.P. and da Fonseca, P.C.A. (2017) “High resolution cryo-EM proteasome structures in drug development”, Acta Crystallogr. D Biol. Crystallogr., 73: 522 533.
  5. Li, H., Bogyo, M., da Fonseca, P.C.A. (2016) “The cryo-EM structure of the Plasmodium falciparum 20S proteasome and its use in the fight against malaria”, FEBS J., 283: 4238 4243.
  6. Li, H., O’ Donoghue, A.J., van der Linden, W.A., Xie, S.C., Yoo, E., Foe, I.T., Tilley, L., Craik, C.S., da Fonseca, P.C.A., Bogyo M. (2016) “Structure- and function- based design of Plasmodium-selective proteasome inhibitors”, Nature, 530: 233 236.
  7. da Fonseca, P.C.A. and Morris, E.P. (2015) “Cryo-EM reveals the conformation of a substrate analogue in the human 20S proteasome core”, Nat. Commun., 6:7573.

Contact

paula.dafonseca@glasgow.ac.uk

---

+++

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. 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.

Contact

Marshall.Stark@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

---

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 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.

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.

Study options

PhD

  • Duration: 3/4 years full-time; 5 years part-time

Individual research projects are tailored around the expertise of principal investigators.

MSc (Research)

  • Duration: 1 year full-time; 2 years part-time

Entry requirements

A 2.1 Honours degree or equivalent.

English language requirements

Subject to confirmation for 2022 entry

For applicants whose first language is not English, the University sets a minimum English Language proficiency level.

International English Language Testing System (IELTS) Academic module (not General Training)

  • 6.5 with no sub-test under 6.0. 
  • Tests must have been taken within 4 years 5 months of start date. Combined scores from two tests taken within 6 months of each other can be considered.

Common equivalent English language qualifications

All stated English tests are acceptable for admission to this programme:

TOEFL (ib, my best or athome)

  • 90 with minimum R 20, L 19, S 19, W 23. 
  • Tests must have been taken within 4 years 5 months of start date. Combined scores from two tests taken within 6 months of each other can be considered.

PTE (Academic)

  • 60 with minimum 59 in all sub-tests.
  • Tests must have been taken within 4 years 5 months of start date. Combined scores from two tests taken within 6 months of each other can be considered.

Glasgow International College English Language (and other foundation providers)

  • 65%.
  • Tests are accepted for academic year following sitting.

University of Glasgow Pre-sessional courses

  • Tests are accepted for academic year following sitting.

Alternatives to English Language qualification

  • Undergraduate degree from English speaking country (including Canada if taught in English)
  • Undergraduate 2+2 degree from English speaking country
  • Undergraduate 2+2 TNE degree taught in English in non-English speaking country
  • Masters degree from English speaking country
  • Masters degree (equivalent on NARIC to UK masters degree) taught in English in non-English speaking country.

For international students, the Home Office has confirmed that the University can choose to use these tests to make its own assessment of English language ability for visa applications to degree level programmes. The University is also able to accept an IELTS test (Academic module) from any of the 1000 IELTS test centres from around the world and we do not require a specific UKVI IELTS test for degree level programmes. We therefore still accept any of the English tests listed for admission to this programme.

Pre-sessional courses

The University of Glasgow accepts evidence of the required language level from the English for Academic Study Unit Pre-sessional courses. We also consider other BALEAP accredited pre-sessional courses:

Fees and funding

Fees

2022/23

  • UK: £4596
  • International & EU: £23,950

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

Alumni discount

We offer a 20% discount to our alumni on all Postgraduate Research and full Postgraduate Taught Masters programmes. This includes University of Glasgow graduates and those who have completed Junior Year Abroad, Exchange programme or International Summer School with us. 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 Scottish Government has confirmed that fees for EU students commencing their studies 2020/21 will be at the same level as those for UK student. 

From 2021/22, new entrant EU students will pay the same fees as all other international students.

Possible additional fees

  • Re-submission by a research student £540
  • Submission for a higher degree by published work £1,355
  • Submission of thesis after deadline lapsed £350
  • Submission by staff in receipt of staff scholarship £790

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.

+++

2021/22 fees

  • UK: £4,500
  • International & EU: £23,000

Additional fees for all students:

  • Re-submission by a research student £540
  • Submission for a higher degree by published work £1,355
  • Submission of thesis after deadline lapsed £350
  • Submission by staff in receipt of staff scholarship £790

---

Funding

The iPhD  is not supported by University of Glasgow Scholarship/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 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.

*iPhD applicants do not need to contact a supervisor, as you will start your programme by choosing a masters from our Taught degree programmes A-Z [do not apply directly to a masters].

Gather your documents

Before applying please make sure you gather the following supporting documentation:

  1. Final or current degree transcripts including grades (and an official translation, if needed) – scanned copy in colour of the original document.
  2. Degree certificates (and an official translation, if needed): scanned copy in colour of the original document
  3. Two references on headed paper and signed by the referee. One must be academic, the other can be academic or professional [except iPhD applicants, where only one academic or professional reference is required]. References may be uploaded as part of the application form or you may enter your referees contact details on the application form. We will then email your referee and notify you when we receive the reference.  We can also accept confidential references direct to rio-researchadmissions@glasgow.ac.uk, from the referee’s university or business email account.
  4. Research proposal, CV, samples of written work as per requirements for each subject area. iPhD applicants do not need to submit any of these as you will start your programme by choosing a masters.

Notes for iPhD applicants

  • add 'I wish to study the MSc in (chosen subject) as the masters taught component of the iPhD' in the research proposal box
  • write 'n/a' for the supervisor name
Apply now

I've applied. What next?

If you have any other trouble accessing Applicant Self-Service, please see Application Troubleshooting/FAQs. 

Contact us

Before you apply

PhD/MSc/MD: email mvls-gradschool@glasgow.ac.uk

iPhD: email mvls-iphd@glasgow.ac.uk

After you have submitted your application

PhD/MSc/MD/iPhD: contact our Admissions team

Any references may be submitted by email to: rio-researchadmissions@glasgow.ac.uk