The Oxford-Percival Stanion Graduate Scholarship
The Oxford-Percival Stanion graduate scholarship is available for applicants who are applying to a full-time DPhil (Phd) course in the Department of Biochemistry, University of Oxford for 2022 entry:
The scholarship covers course fees, college fees and a grant for living costs for full-time students of at £15,609. Awards are made for the full duration of your fee liability for the DPhil.
The scholarship is jointly funded by the University and a generous endowment from PERCIVAL STANION, an alumnus of Pembroke College where he was an undergraduate in the 1970s, and a member of the Pembroke Master's Circle as well as of its Investment Committee.
The scholarship is only tenable at Pembroke College, and a close match of research interests with the Pembroke Biochemistry Fellow, Associate Professor Andre Furger, is highly desirable.
Pembroke College is a lively academic community based in the centre of Oxford. Professor Andre Furger leads a high-achieving and close-knit group of biochemists here, including undergraduates and visiting students as well as graduate students and lecturers. The college has a vibrant and supportive graduate community made up of more than 250 graduate students and offers a range of benefits to graduates, including a range of accommodation graduates can apply for, including self-contained flats for couples. Pembroke graduates also have the opportunity to apply to the Dean of Graduates' fund for financial support for conference attendance and travel costs. For more information about the graduate community in Pembroke College and Pembroke Graduate accommodation, follow the links below:
Pembroke Graduate Community Pembroke Accommodation Pembroke College
FURGER LAB RESEARCH
Key words: mRNA metabolism, Circadian Rhythm, Controlled Cooling, Control of gene expression,
pre-mRNA processing, alternative polyadenylation, RNA Therapeutics
The research in the Furger laboratory broadly focusses on mRNA metabolism in human cells under stress conditions and during disease progression. We currently focus on how cells reprogram gene expression at the transcriptional, co-transcriptional and post-transcriptional level when they are exposed to cold stress, viral infection and during cancer progression and how these changes affect cell physiology. To understand these processes we use a wide range of methodologies including high resolution microscopy, functional genomics approaches and cell biology and work closely with a number of longstanding national and international collaborators.
1) Alternative Cleavage and Polyadenylation during cellular stress and disease progression
A hallmark of eukaryotic gene expression is the co-transcriptional processing of primary protein encoding transcripts by capping, splicing and cleavage and polyadenylation resulting in mature functional mRNAs. Cleavage and polyadenylation defines the end of almost all mRNAs, creating their characteristic poly-adenosine tails. Most human genes have multiple polyA sites and alternative usage (alternative cleavage and polyadenylation or APA) of these sites enables cells to produce mRNA isoforms that differ in the length of their 3' untranslated regions (3'UTR). APA plays an important role in the regulation of gene expression during cellular differentiation, disease progression and in response to stress. We aim to understand how cold shock and viral infections influence regulators of alternative cleavage and polyadenylation, and how the change in the mRNA isoform landscape affects cell physiology.
DPhil projects are available that:
Aims to understand how viral encoded proteins influence polyA site choice in host cells and how this affects the host immune response.
Aims to understand how cold shock activates specific factors that regulate alternative cleavage and polyadenylation and how this protects cells from the destructive effects of cooling.
hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles. Fischl H, Neve J, Wang Z, Patel R, Louey A, Tian B, Furger A. Nucleic Acids Res. 2019 Aug 22;47(14):7580-7591. doi: 10.1093/nar/gkz461
Alternative cleavage and polyadenylation of genes associated with protein turnover and mitochondrial function are deregulated in Parkinson's, Alzheimer's and ALS disease.
Patel R, Brophy C, Hickling M, Neve J, Furger A. BMC Med Genomics. 2019 May 9;12(1):60. doi: 10.1186/s12920-019-0509-4.
Cleavage and polyadenylation: Ending the message expands gene regulation.
Neve J, Patel R, Wang Z, Louey A, Furger AM. RNA Biol. 2017 Jul 3;14(7):865-890. doi: 10.1080/15476286.2017.1306171
2) Molecular Characterisation of the Human Cold Shock Response: "Cooling the Cellular Clock"
Controlled cooling is widely used in a number of medical applications principally to reduce the metabolic needs of cells when the blood supply to tissues and organs is restricted and oxygen becomes scares. Cold temperature exposure has additional medical benefits but the underlying molecular processes are largely unknown. The Furger lab has recently addressed this issue by systematically characterising gene expression responses and structural changes that are associated with cooling and subsequent rewarming of cells. This research identified a previously unknown link between very low temperatures and the resetting of the circadian clock. The circadian clock is a cell autonomous time keeper that at the molecular level is driven by interconnecting transcription and translation feet-back loops that are created by products of the core clock genes regulating their own rhythmic expression. The oscillating core clock genes encode transcription factors that also regulate the expression of thousands of genes and so align the physiology of the cells, organs and behaviour of organisms with the 24h day and night cycle of the earth. We aim to understand the molecular processes and factors that are activated by cooling and force the reset of the circadian clock upon rewarming of the cells. As the circadian clock regulates fundamental cellular processes and is critical to health, it is of great importance to understand how the circadian clock can be manipulated.
DPhil projects are available that:
1) Aims to unravel how structural changes molecular mechanisms that are activated by cooling and rewarming, affect the transcription and translation feedback loops of the core clock genes and force a resetting of the circadian clock.
- Cold-induced chromatin compaction and nuclear retention of clock mRNAs resets the circadian rhythm. Fischl H, McManus D, Oldenkamp R, Schermelleh L, Mellor J, Jagannath A, Furger A. EMBO J. 2020 Nov 16;39(22):e105604. doi: 10.15252/embj.2020105604.
2) RNA Therapeutics
We have recently started a new research avenue where we use our expertise in RNA metabolism and RNA structure and function to design RNA therapeutics. The DPhil project will be multidisciplinary and more details are available by directly contacting Prof. Furger.
What do the projects offer?
The projects offer training in a wide range of state of the art methodologies including, super resolution microscopy, high through-put sequencing technologies, bioinformatics, in vitro mRNA production, tissue culture, cell biology and classic biochemistry and molecular biology techniques.
All projects are best suited to highly motivated applicants wanting to work in a supportive, collaborative and multidisciplinary environment.
BBSRC PhD Studentship in Synthetic biology engineering of Spy-protein pairs towards targeting of viral vectors for gene therapy and vaccination [Project 2022/05]
About the Project
In collaboration with Oxford Biomedica.
A major challenge for viral vectors is that their beneficial effects often depend on the transduction of one celltype, whereas transduction of other cell-types may lead to harmful side-effects. New approaches are needed to address this challenge, to help fulfil the enormous potential of viral vectors for different areas of gene therapy and vaccine generation. SpyTag is a peptide that forms a spontaneous covalent bond to its protein partner SpyCatcher, previously developed by the Howarth group. Both SpyTag and SpyCatcher are genetically encodable and form an amide bond simply upon mixing together. SpyTag and SpyCatcher allow viral vectors to be irreversibly decorated with a specific targeting group (e.g. an antibody or a nanobody), towards enhanced infection of a specific cell-type of interest. In this project we will use innovative methods in rational protein engineering and directed evolution, to generate new SpyTag/SpyCatcher pairs to advance the potential of this approach. This includes new switchable versions of the pair for controlled capture and release, to facilitate clinical production and development of viral vectors. We will also apply innovative methods for nanoparticle analysis, harnessing mass photometry pioneered in the Kukura group, to give unique insight from single molecule investigation of re-decorated viral particles. Working with Oxford Biomedica, we will enhance the retargeting of the viral vectors for specific transduction of different cell-types, with the overall goal of establishing a powerful approach for increasing the activity and safety of viral vectors.
Skills training will be provided in molecular biology, protein design, directed evolution, mass photometry, cell biology, fluorescence microscopy, and bioinformatics. According to the development of the project, there may also be the chance to learn structure determination by X-ray crystallography.
Please see https://www.findaphd.com/phds/project/bbsrc-phd-studentship-in-synthetic-biology-engineering-of-spy-protein-pairs-towards-targeting-of-viral-vectors-for-gene-therapy-and-vaccination-project-2022-05/?p140234 for further information