Engineering CRISPR-Cas Nucleases for Accessible Diagnostics and Sensing

About the Project

CRISPR-Cas12 and Cas13 are families of enzymes are RNA-guided nucleases that sequence-selectively cleave nucleic acids that are complementary to an RNA strand that is pre-loaded on to these nucleases^[1,2]. In addition, upon activation of the CRISPR-Cas complex, both Cas12 and Cas13 exhibit trans-cleavage activity, the collateral cleavage of non-target sequences that are nearby.

This selective activation of CRISPR-Cas12 and Cas13 coupled with the nonspecific trans-cleavage activity has potential use in the detection of DNA or RNA sequences that are of interest, since the enzyme could act as both the identification mechanism and the signal amplifier for various readout methods^[3]. Previous work has utilized CRISPR-Cas12 and CRISPR-Cas13 enzymes for identification of bacteria, miRNAs, and parasites^[4–7].

The research is aimed at recombinantly engineering Cas12 and Cas13 proteins for practical applications in diagnostics and genotyping. For this purpose, investigations will be carried out into the structure and mechanism of these nucleases, and their biophysical behaviour under assay-relevant conditions. In parallel, mutagenic engineering will undertaken to optimise the enzymes for these applications.

Candidates should have an interest in one or more of the following areas: structural biology, molecular biology, molecular genetics, enzymology or biophysics; and is interested in developing a range of new skills. This work will equip the successful candidate expertise that are critical for the industrial biotechnology sector – the ability to rationally engineer new, high-value biotechnological products through fundamental insights in biomolecular structure and practical biochemistry.

The successful candidate will join a growing team of multidisciplinary researchers from a range of backgrounds in chemistry and biology. The research is based at the Manchester Institute of Biotechnology (www.mib.ac.uk) and the university’s Genome Editing Unit, both of which offer state-of-the-art laboratories, instrumentation and facilities. The project will be supervised by a collaborative supervisory team including Drs. Lu Shin Wong, Antony Adamson and Prof. William Newman. Informal enquiries can be directed at the supervisor Dr. Lu Shin Wong (research.manchester.ac.uk/en/persons/l.s.wong).

Eligibility

Applicants must have (or expect to achieve) at least an upper second class honours degree, or the equivalent, from a reputable institution; in biochemistry, molecular biology, structural biology, genetics, or a relevant related subject.

Funding

At Manchester we offer a range of funding through scholarships, studentships and other awards. Outstanding students will be nominated for the relevant award, and assistance with applying for externals scholarships.

Before you apply

We strongly recommend that you contact the supervisor for this project before you apply. Please include details of your current level of study, academic background and any relevant experience and include a paragraph about your motivation to study this PhD project.

How to apply

Apply online through our website: https://uom.link/pgr-apply-2425

When applying, you’ll need to specify the full name of this project, the name of your supervisor, if you already having funding or if you wish to be considered for available funding through the university, details of your previous study, and names and contact details of two referees.

Your application will not be processed without all of the required documents submitted at the time of application, and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.

After you have applied you will be asked to upload the following supporting documents:

• Final Transcript and certificates of all awarded university level qualifications
• Interim Transcript of any university level qualifications in progress
• CV
• Supporting statement: A one or two page statement outlining your motivation to pursue postgraduate research and why you want to undertake postgraduate research at Manchester, any relevant research or work experience, the key findings of your previous research experience, and techniques and skills you’ve developed. (This is mandatory for all applicants and the application will be put on hold without it).
• Contact details for two referees (please make sure that the contact email you provide is an official university/work email address as we may need to verify the reference)
• English Language certificate (if applicable)

If you have any questions about making an application, please contact our admissions team by emailing FSE.doctoralacademy.admissions@manchester.ac.uk.