Background
Many viruses bind and enter cells using protruding spike proteins that interact with host proteins and cellular membranes to mediate infection. Viral spikes are prime targets for host immune responses, and antibodies that bind and block critical spike functions are known as neutralizing antibodies, which can prevent infection. In addition, as spikes are unambiguous markers of viral infection, the specificity of spike-antibody interactions have been exploited in terms of disease diagnostics, with spike antibodies forming the basis for diagnostic tests such as lateral flow devices (LFDs) that are familiar objects in the COVID-19 era.
Affimers are renewable, recombinant, molecular recognition reagents with diverse applications within molecular and cellular biology, including the study of protein localization, protein function and protein-protein interactions.
Affimer production is highly scalable and reproducible, and combined with their high stability and target specificity, they represent excellent alternative non-antibody tools for the development of molecular detection assays, such as point-of-care LFDs.
Objective
Focusing on selected viruses listed on the World Health Organization (WHO) R&D blueprint (Lassa, Ebola, Rift Valley fever and Crimean-Congo hemorrhagic fever viruses) we will isolate Affimers that bind their respective spike proteins and other relevant proteins such as nucleoproteins, with the aim of developing a multiplexed pathogen detection platform for the diagnosis and differentiation of the corresponding diseases. Development of an Affimer- based diagnostic platform would meet the challenge of the WHO R&D blueprint, and also break the reliance on animal-based antibody production, which is a goal of the BBSRC transformative technologies priority.
The spike-specific Affimers we generate will be also assessed for their ability to neutralize virus infectivity. Structural and functional studies of the spike- Affimer complex will be performed to dissect the molecular basis for neutralization, with the potential to identify sites critical for spike function.
Novelty
While antibodies remain the most widely used molecular recognition reagent, some are poorly characterized, take a long time to harvest and/or have stability or batch variability issues, supporting the development and use of alternative binding proteins such as Affimers as complementary reagents for many applications and provide highly specific binding (PNAS, NSMB, eLife, Nature Comms). Affimer production is consistent and scalable, which are significant advantages in the generation of diagnostics especially when the targeted diseases occur in countries with low investment in health infrastructure and delivery, as is the case with the viruses named above.
This project will be delivered in partnership with Mologic. If a student is recruited, the project will be converted to an i-CASE (industry partnership) following the start date of October 2022.
Funding Note
This studentship is part of the BBSRC White Rose Doctoral Training Partnership in Mechanistic Biology. (https://www.whiterose-mechanisticbiology-dtp.ac.uk/). Appointed candidates will be fully-funded for 4 years. The funding includes:
Tax-free annual UKRI stipend (£15,609 for 2021/22 starts. Awards increase every year, typically with inflation).
UK tuition fees (Around £4,500 per year)
Research Training and Support Grant (RTSG)
Conference and Professional Internships for PhD Students (PIPS) allowances
We aim to support the most outstanding applicants from inside and outside the UK. We are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.
Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.
How to apply
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).
To help us identify that you are applying for this studentship 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
- For source of funding please state you are applying for a White Rose BBSRC DTP funded studentship
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