Postgraduate Research Opportunity

Development of novel cancer treatments: structural studies of Nectin 4 in complex with bespoke anti-cancer peptides

Details

Title: Development of novel cancer treatments: structural studies of Nectin 4 in complex with bespoke anti-cancer peptides

Funding: Full time Home/EU fees (£4630)

Application deadline: 1 July 2019

Start date: October 2019

Duration: 1 year (full time)

Location: Colchester Campus

Based in: School of Biological Sciences

Please note that this studentship is for a one year Master of Science by Dissertation (MSD), not a PhD.

Scientific background

This project targets the current gap in therapeutic approaches targeting Triple Negative Breast Cancer (TNBC) that, unlike other breast cancer subtypes, lacks recommended chemotherapy treatment.

Recent studies suggest that Nectin-4 is a promising target for the treatment of TNBC. Nectin-4 is expressed during foetal development, with expression declining in adult life, and it is re-expressed as a tumour-associated antigen with pro-oncogenic properties in TNBC and other cancers, including Bladder Cancer and Lung Cancer. Thus, Nectin-4 is both a promising new prognostic biomarker and specific therapeutic target for the treatment of TNBC. 

Studies on patient samples show that Nectin-4 is highly expressed in cancer tissues, but is not detectable in healthy ones. The hypothesis is that targeting Nectin-4 with a peptide conjugated with toxin could provide a novel treatment for TNBC.

Novel compounds designed at our collaborators – Bicycle Therapeutics - are targeting Nectin-4 specifically at nanomolar range and can potentially be used as homing devices, having shown success in in vitro cell assays. However their mechanism of action and exact domain tropism is unknown.

Research methodology

In collaboration with Bicycle Therapeutics, we aim to solve the crystal structure of the extracellular domain of Nectin-4 bound to these proprietary cyclic peptides, which will guide further optimisation of the peptide before preclinical and clinical studies.

Training

The student will express and purify recombinant proteins using bacterial expression system. The student will produce protein crystals suitable for investigation using X-Ray crystallography with the aim of solving the structure of the Nectin-4 extracellular domain bound to different bicycle peptides provided by Bicycle Therapeutics.

In addition to hands-on practical research skills at University of Essex, the student will attend the Diamond Light Source BAG training courses and participate in data collection and processing.

This project is highly interdisciplinary and involves a high-profile industrial collaboration, plus the student will benefit from an international environment in close contact with two PhD students and two PDRA engaged in related drug discovery projects.

Furthermore, if successful, this highly translational research has the potential to lead to a 3-year PhD scholarship.

Funding

The award consists of a full Home/EU fee waiver or equivalent fee discount for overseas students (further fee details), plus £1,000 training bursary via Proficio funding, which may be used to cover the cost of advanced skills training including conference attendance and travel.

Criteria

Candidates should have a background in biochemistry and an interest in structural biology.

How to apply

You can apply for this postgraduate research opportunity online.

Instruction to applicants

When you apply online you will be prompted to fill out several boxes in the form:

  • For "Course title" please put "Master of Science by Dissertation, Biological Sciences"
  • For "Proposed research topic or area of research" please put the title of this studentship (Development of novel cancer treatments: structural studies of Nectin 4 in complex with bespoke anti-cancer peptides)
  • For "If you have contacted a potential supervisor..." please put the name of the lead supervisor (Dr Filippo Prischi)

If you have any informal queries about this opportunity please email the supervisors, Dr Filippo Prischi (fprischi@essex.ac.uk) and Dr Vassily Bavro (v.bavro@essex.ac.uk)

If you have any queries about the online application please contact Emma Revill (ecrix@essex.ac.uk)