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Cryo-electron microscopy of influenza virus and bunyaviruses


   Faculty of Biological Sciences


About the Project

As demonstrated by SARS-CoV-2, viruses have the potential to cause devastating economic and healthcare disruption on a global scale. We are interested in several structural aspects of influenza virus and bunyaviruses, both of which are negative-stranded RNA viruses.

Influenza virus is a current public health risk. 5-10% of adults are yearly affected by seasonal Influenza outbreaks, leading to up to 5 million cases of severe illness and 500,000 deaths worldwide. Additionally, Influenza can develop resistance to current antivirals and new strains can emerge and result in pandemics. We are interested in two aspects of the influenza virus replication cycle: 1) how influenza starts an infection within a cell, a process that requires the merging (fusion) of the viral and cellular membranes mediated by the viral hemagglutinin protein; and 2) how influenza’s 8 RNA segments bundle together to form an infectious particle, potentially resulting in novel pandemic influenza viruses. We are also developing strategies to detect and block influenza virus infections, by using a novel type of antibody-like proteins, termed Affimers.

On the other hand, bunyaviruses are emerging RNA viruses that cause significant disease and economic burden and for which vaccines or therapies approved for human use do not exist. We are interested in 3 aspects of the bunyavirus life cycle: 1) We have studied the requirement of endosomal ions for enveloped virus fusion and found that K+ ions induce conformational changes in the viral fusion proteins of bunyaviruses, enhancing interactions with the target membrane. 2) We aim to understanding the structure of the viral genome, which is wrapped up by the nucleoprotein (NP) to form a flexible chain called a ribonucleoprotein (RNP). And 3) we aim to understand how the virus remodels the cell host membranes in order to establish replication factories.

To answer these research questions we employ a combination of state-of-the-art electron microscopy (including cryo-electron microscopy and correlative light-electron microscopy) and molecular biology.

Applications are welcomed from self-funded students or from students who have a sponsor who will provide their funding.

Eligibility: 

You should hold a first degree equivalent to at least a UK upper-second class honours degree or a MSc degree in a relevant subject. This project would suit someone with a strong background in tissue engineering, cancer biology or closely-related areas. Additional experience of conducting research in a multidisciplinary setting is highly desirable. Upon completion of the PhD, the successful candidate will be uniquely equipped for high-demand careers within academia or industry with desirable skills in bioengineering, regenerative medicine and cancer/cell biology.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Biological Sciences minimum requirements in IELTS and TOEFL tests are:

  • British Council IELTS - score of 6.0 overall, with no element less than 5.5
  • TOEFL iBT - overall score of 87 with the listening and reading element no less than 20, writing element no less than 21 and the speaking element no less than 22.

How to apply:

To apply for this project applicants should complete an online application form and attach the following documentation to support their application. 

  • a full academic CV
  • degree certificate and transcripts of marks
  • Evidence that you meet the University's minimum English language requirements (if applicable).
  • Evidence of funding

To help us identify that you are applying for this project please ensure you provide the following information on your application form;

  • Select PhD in Biological Sciences as your programme of study
  • Give the full project title and name the supervisors listed in this advert

To find out more about the research in Dr Juan Fontana’s lab, you can email


Funding Notes

International or home self-funded or scholarship/fellowship PhD students are welcome to apply. Bench fees will be required. International applicants who are not native English speakers must meet the minimum English language entry requirement (IELTS 6.0 overall with at least 5.5 in each component or equivalent). Applications can be made throughout the year.

References

Ion Channels as Therapeutic Targets for Viral Infections: Further Discoveries and Future Perspectives. Charlton FW, Pearson HM, Hover S, Lippiat JD, Fontana J, Barr JN, Mankouri J.Viruses. 2020;12(8):844. doi: 10.3390/v12080844. PMID: 32756358
The RNA Replication Site of Tula Orthohantavirus Resides within a Remodelled Golgi Network.
Davies KA, Chadwick B, Hewson R, Fontana J, Mankouri J, Barr JN.
Cells. 2020 Jun 27;9(7):1569. doi: 10.3390/cells9071569.
Potassium is a trigger for conformational change in the fusion spike of an enveloped RNA virus. Punch EK, Hover S, Blest HTW, Fuller J, Hewson R, Fontana J, Mankouri J, Barr JN.J Biol Chem. 2018;293(26):9937-9944. doi: 10.1074/jbc.RA118.002494. PMID: 29678879
Bunyavirus requirement for endosomal K+ reveals new roles of cellular ion channels during infection. Hover S, Foster B, Fontana J, Kohl A, Goldstein SAN, Barr JN, Mankouri J.PLoS Pathog. 2018;14(1):e1006845. doi: 10.1371/journal.ppat.1006845. PMID: 29352299
The Fusion Loops of the Initial Prefusion Conformation of Herpes Simplex Virus 1 Fusion Protein Point Toward the Membrane. Fontana J, Atanasiu D, Saw WT, Gallagher JR, Cox RG, Whitbeck JC, Brown LM, Eisenberg RJ, Cohen GH.mBio. 2017 Aug 22;8(4):e01268-17. doi: 10.1128/mBio.01268-17. PMID: 28830949

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