Back to search results

PhD Studentship: High-throughput discovery of lysine-directed probes for protein kinases

University of Leeds - Faculty of Engineering and Physical Sciences

Qualification Type: PhD
Location: Leeds
Funding for: UK Students
Funding amount: full academic fees, together with a tax-free maintenance grant at the standard UKRI rate (£19,237 in academic session 2024/25) for 3.5 years
Hours: Full Time
Placed On: 4th November 2024
Closes: 10th January 2025

School/Faculty: Chemistry

Closing Date: 10 January 2025

Eligibility: UK Only

Funding:

School of Chemistry Studentship, in support of the EPSRC Research Grant APP5370: A general chemical approach to lysine-directed probes for protein kinases, providing the award of full academic fees, together with a tax-free maintenance grant at the standard UKRI rate (£19,237 in academic session 2024/25) for 3.5 years.

Lead Supervisor’s full name & email address

Professor Adam Nelson: a.s.nelson@leeds.ac.uk

Co-supervisors' full names & email addresses

Dr Megan Wright: m.h.wright@leeds.ac.uk

Professor Richard Bayliss: r.w.bayliss@leeds.ac.uk

Project summary

The resurgence of covalent drug discovery has yielded FDA-approved drugs in therapeutic areas as diverse as cancer, virology and sickle cell anaemia. Irreversible inhibitors usually target a nucleophilic cysteine, a strategy whose success relies on the presence of a suitable residue that is not susceptible to mutation. In the case of the protein kinases, the conserved lysine residue that is intimately involved in phosphotransfer provides a major and undertapped opportunity for the discovery of new drugs and chemical probes.

In this project, we will harness a high-throughput approach to discover covalent probes that target the conserved lysine in protein kinases.  The student will develop plate-based chemistry in which pairs of building blocks will be combined to yield diverse probe sets.  The probe sets will be exploited to discover novel covalent modifiers of specific protein kinases.  The student will harness a chemical proteomic approach to profile the proteome-wide reactivity of the discovered probes; and exploit biochemical and structural biology approaches to characterise their mechanism of action.

The studentship will take advantage of the outstanding research environment of the Astbury Centre for Structural Molecular Biology, including cutting-edge structural biology and chemical proteomics capabilities.

The specific objectives of the project will be:

  1. To develop high-throughput chemistry to enable the synthesis of diverse lysine-directed kinase probes
  2. To harness high-throughput experimentation to discover novel covalent modifiers of specific protein kinases
  3. To characterise the mechanism of discovered probes using chemical proteomic, biochemical and structural biology approaches.

Please state your entry requirements plus any necessary or desired background

A first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline.

Subject Area: Biochemistry, organic chemistry, synthetic chemistry

Keywords: Chemical biology, structural biology, biochemistry, organic synthesis 

We value your feedback on the quality of our adverts. If you have a comment to make about the overall quality of this advert, or its categorisation then please send us your feedback
Advert information

Type / Role:

Subject Area(s):

Location(s):

PhD tools
 

PhD Alert Created

Job Alert Created

Your PhD alert has been successfully created for this search.

Your job alert has been successfully created for this search.

Ok Ok

PhD Alert Created

Job Alert Created

Your PhD alert has been successfully created for this search.

Your job alert has been successfully created for this search.

Manage your job alerts Manage your job alerts

Account Verification Missing

In order to create multiple job alerts, you must first verify your email address to complete your account creation

Request verification email Request verification email

jobs.ac.uk Account Required

In order to create multiple alerts, you must create a jobs.ac.uk jobseeker account

Create Account Create Account

Alert Creation Failed

Unfortunately, your account is currently blocked. Please login to unblock your account.

Email Address Blocked

We received a delivery failure message when attempting to send you an email and therefore your email address has been blocked. You will not receive job alerts until your email address is unblocked. To do so, please choose from one of the two options below.

Max Alerts Reached

A maximum of 5 Job Alerts can be created against your account. Please remove an existing alert in order to create this new Job Alert

Manage your job alerts Manage your job alerts

Creation Failed

Unfortunately, your alert was not created at this time. Please try again.

Ok Ok

Create PhD Alert

Create Job Alert

When you create this PhD alert we will email you a selection of PhDs matching your criteria.When you create this job alert we will email you a selection of jobs matching your criteria. Our Terms and Conditions and Privacy Policy apply to this service. Any personal data you provide in setting up this alert is processed in accordance with our Privacy Notice

Create PhD Alert

Create Job Alert

When you create this PhD alert we will email you a selection of PhDs matching your criteria.When you create this job alert we will email you a selection of jobs matching your criteria. Our Terms and Conditions and Privacy Policy apply to this service. Any personal data you provide in setting up this alert is processed in accordance with our Privacy Notice

 
 
 
More PhDs from University of Leeds

Show all PhDs for this organisation …

More PhDs like this
Join in and follow us

Browser Upgrade Recommended

jobs.ac.uk has been optimised for the latest browsers.

For the best user experience, we recommend viewing jobs.ac.uk on one of the following:

Google Chrome Firefox Microsoft Edge