World-Leading St Andrews Scholarship in Biochemistry2021 entry
The University of St Andrews is pleased to offer a full scholarship funded by St Leonard’s Postgraduate College, to support an exceptional student undertaking doctoral research in the following project:
Visualising SARS-CoV-2 Fusing to Host Cells Using Single-Molecule Microscopy
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The worldwide emergence and rapid spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has caused more than 1.5 million deaths and infected more than 70 million people worldwide, putting healthcare systems at the border of collapse and the entire economy into recession. Compared to other members of the SARS family, including SARS-CoV and MERS (Middle East Respiratory Syndrome), SARS-CoV-2 exhibits a higher transmission rate and evades the human immune system more efficiently. The first step in viral infection is the attachment of the viral particle to the surface of the host cell, subsequently enter endosomes, and eventually fusing viral and lysosomal membranes. Understanding how SARS-CoV-2 infects cells is a high priority and the first opportunity to develop intervention strategies. This project will investigate how SARS-CoV-2 enters the host cell by fusing its viral envelope to the host cell membrane. We will develop a combination of biomimetic proteo-liposomes and single-molecule methods to dissect each step of the membrane fusion mechanism in real time.
In the case of SARS-CoV and SARS-CoV-2, it has been shown that a virus surface-anchored spike protein, so called S protein, mediates coronavirus entry by recognizing angiotensin-converting enzyme 2 (ACE2) in the surface of the host cell. It has been demonstrated that after initial binding to the ACE2 receptor via its S1 domain, the spike protein is activated by cleavage at the S1/S2 boundary by host cell proteases. This results in S1 dissociation, whereas the S2 domain undergoes major conformational changes that enable membrane fusion. The major proteases involved in the two SARS-CoV are transmembrane protein serine 2 (TMPRSS2), cathepsins and furin-like proteases3.
To date, the characterization of viral invasion has focused on the spike-ACE2 interaction. In contrast, very little is known about the actual entry mechanism from the perspective of the interacting membranes. In this project we will fill this gap by shedding light into key SARS-CoV-2 unknowns including: what are the steps involved in membrane fusion? what is the nature of any partially-fused state and the timescale of fusion? How does the density of anchored complexes impact the process and what is the role of spike cleavage?
We will use proteo-liposomes as biomimetic systems for in vitro studies, and to mimic viral particles fusing to selected cells expressing the ACE2 receptor, for in vivo studies. We will employ a single-molecule fluorescence resonance energy transfer assay (smFRET) to visualize the in real time the mechanism of viral entry to the host cell.
The student will be supervised by Dr Carlos Penedo (School of Biology and School of Physics and Astronomy), Dr Juan Varela (School of Biology), and Professor Terry Smith (School of Biology and School of Chemistry). The project is highly inter-disciplinary and combines elements of biophysics, molecular biology, virology and state-of-the-art optical imaging single-molecule techniques, thus providing an unique training environment for the student. The student will also have the opportunity to benefit from working at the interface between three Schools (Physics and Astronomy, Biology, Chemistry), participate in seminars and training courses across these disciplines, and use the exceptional imaging and laser facilities available at the Centre of Biophotonics (https://synergy.st-andrews.ac.uk/cob/).
Informal enquiries regarding this scholarship may be addressed to Dr Carlos Penedo (jcp10@st-andrews.ac.uk) and to Dr Juan Varela (jv32@st-andrews.ac.uk).
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Geographical criteria
No restrictions.
Domicile for fee status
No restrictions.
Level of study
Postgraduate Research (Doctoral)
Year of entry
2021-2022 academic year
The student can start their degree in August 2021 or September 2021.
Schools
School of Biology
Additional criteria
Applicants must not already (i) hold a doctoral degree; or (ii) be matriculated for a doctoral degree at the University of St Andrews or another institution.
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Duration of award
Up to 3.5 years. The successful candidate will be expected to have completed the doctorate degree by the end of the award term. The award term excludes the continuation period and any extension periods.
Value of award
The award covers full tuition fees for the award term as well as an annual stipend payable at the standard UK Research Council rate (the 2021-22 annual rate is £15,560).
Tuition or maintenance award
Tuition and maintenance.
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Doctoral Research at St Andrews
As a doctoral student at the University of St Andrews you will be part of a growing, vibrant, and intellectually stimulating postgraduate community. St Andrews is one of the leading research-intensive universities in the world and offers a postgraduate experience of remarkable richness.
St Leonard’s Postgraduate College is at the heart of the postgraduate community of St Andrews. The College supports all postgraduates and aims to provide opportunities for postgraduates to come together, socially and intellectually, and make new connections.
St Leonard’s Postgraduate College works closely with the Postgraduate Society which is one of the most active societies within the Students’ Association. All doctoral students are automatically welcomed into the Postgraduate Society when they join the University.
In addition to the research training that doctoral students complete in their home School, doctoral students at St Andrews have access to GRADskills – a free, comprehensive training programme to support their academic, professional, and personal development.
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- Apply for admission as a doctoral student. Please see the advice on Research programmes.
- After you have applied for your chosen Postgraduate Research course, you can apply for scholarships and funding by logging into My Application. After applying for your chosen course beginning in the 2021-2022 academic year, you must allow at least two working days for processing and issue of your log in details before you can apply for this scholarship.
- Select 2021/2 as the Academic Year and click Refresh list.
- Locate World-Leading St Andrews Doctoral Scholarships in the list of scholarships (using the filter box if necessary), click Apply and complete the application form.
- You can also use the catalogue to search and apply for other scholarships for which you are eligible.
If you are a current student at St Andrews, you can access Scholarships and Funding through MySaint. However, you should wait until after you have applied for your intended postgraduate programme before doing so, to ensure that the scholarship application is linked to that course.
As part of the scholarship application you will be required to upload a personal statement. This should serve as a cover letter for the research project application as a whole, and should include:
- An outline of your suitability for the project (project criteria can be found in the "Eligibility" and "Project Description" sections above).
- Why the project interests you.
- What you would bring to the project in terms of previous skills and expertise.
- Any ideas that you may have for the realisation of the project.
Please contact pgscholarships@st-andrews.ac.uk with any enquiries about the scholarship application process.
When do applications open?
December 2020
Scholarship application deadline
26 February 2021
When should I apply for the scholarship?
Apply for the scholarship as soon as possible after you have applied for admission.
When will I hear if my application has been successful?
Within two months of the application deadline.