Developing chemical probes to distinguish CDK4-cyclin D

Number of awards
1

Start date and duration
October 2020 for four years

Overview
CDK4/6 inhibitors have been approved to treat hormone responsive/HER2 negative breast cancer. CDK4 and CDK6 have different cellular roles providing a rationale to develop chemical probes to distinguish them. This project aims to identify and characterise novel protein binding sites that distinguish CDK4 and CDK6, to exploit this knowledge to develop CDK4-selective chemical probes, and to use them to assess the effectiveness of CDK4 vs CDK6-specific inhibition. This studentship will provide an invaluable opportunity to gain experience of the chemistry/biology interface that underpins modern drug discovery. Techniques will include recombinant protein expression/purification and biophysical assays; macromolecular structural studies including X-ray crystallography and computational docking; generation and screening of genetically encoded libraries; and studies to probe mechanism of action of small molecule inhibitors and cyclic peptides in cell line models.

Sponsor
Cancer Research UK

Name of supervisor(s)
Professor J. Endicott (https://bit.ly/2wW2SrH), Faculty of Medical Sciences, Translational and Clinical Research Institute (https://bit.ly/3aRuBZl) (NUTCRI)

Professor A. Kawamura (https://bit.ly/3aXTGSJ), School of Natural and Environmental Sciences (https://bit.ly/2Qb1msM), Chemistry

Professor I. Hickson (https://bit.ly/2xBei4H), NUTCRI.

Eligibility Criteria
You must have or expect to achieve a BSc in an appropriate biochemistry/biological sciences discipline at first or 2:1 level, or a Masters degree in a relevant subject (e.g. cancer research, biochemistry).

You must also achieve IELTS 6.5 overall (with a minimum of 5.5 in all other sub-skills).

How to apply
You must apply through the University’s online postgraduate application system by creating an account. To do this please select ‘How to Apply’ (https://bit.ly/2TKRZ5e) and choose the ‘Apply now’ button.

All relevant fields should be completed, but fields marked with a red asterisk must be completed. The following information will help us to process your application. You will need to:

click on programme of study
insert 8300F in the programme code section and click search
select Programme name ‘PhD in the Faculty of Medical Sciences (full time) – Cancer Research
insert TC006 in the studentship/partnership reference field
attach a covering letter and CV. The covering letter must state the title of the studentship, quote reference code TC006 and state how your interests and experience relate to the project
attach degree transcripts* and certificates and, if English is not your first language, a copy of your English language qualification.
*You will not be able to submit your application until you have submitted your degree transcript/s.

You should also send your covering letter and CV to Jane Endicott by email to: [Email Address Removed]

* The online application system will only allow one application using the programme code 8300F. If you are applying for TWO or more projects using that code then you will need to email our Postgraduate Admissions Service ([Email Address Removed]) with the following information:

your application number (from the first project application that you submitted online)
the second studentship code and its corresponding title
a two page covering letter for the second project.
Our Postgraduate Admissions Service (https://bit.ly/2Qs0vnN) will then forward this information to the relevant selector in the Faculty of Medical Sciences.

Contact
Jane Endicott. E-mail: [Email Address Removed]