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GCDC: Identification of the cellular targets of the Malaysian phytochemical pentamethoxyflavone

Annual Tuition fees at the UKRI Home/EU rate (£4,260 in 2018/19) plus annual stipend at UKRI rates (£14,777 in 2018/19)

This scholarship competition is open to all new postgraduate research applicants.

GCDC scholars will receive the following for 3.5 years:
- Annual stipend at UKRI rates (these were £14,777 in 2018/19);
- Annual tuition fees at UKRI Home/EU rates (these were £4,260 in 2018/19);
- A minimum research training support grant of £3,500; and
- Specialised interdisciplinary GCDC cohort training activities.

GCDC Project-led Studentship - School of Physical Sciences & School of Biosciences: Identification of the cellular targets of the Malaysian phytochemical pentamethoxyflavone, a candidate agent for the chemoprevention of colorectal cancer



Location
School of Physical Sciences and School of Biosciences, University of Kent, Canterbury, with placements at Universiti Malaysia Sarawak, Malaysia

Background
The incidence of colorectal cancer (CRC) has risen at an alarming rate in Malaysia, becoming the second most common cancer in males and third most common in females. Other southeast Asian Lower and Middle Income Countries (LMICs) show a similar profile, and CRC is now an area of unmet medical need in the region.
Our collaborator in Malaysia, Dr Isabel Lim Fong (Universiti Malaysia Sarawak), has discovered that pentamethoxyflavone (PMF), a compound isolated from the common Malaysian plant Orange Jasmine (Murraya paniculata), can kill both precancerous and cancerous colon cells in vitro. It will also prevent progression of colon polyps into CRC in vivo, an effect known as cancer chemoprevention. The cellular target(s) of this chemoprevention activity are unknown, and their identification is critical as it will allow the generation of a more potent and selective PMF-like molecule with optimised drug-like properties ready for clinical trial.

Project Aim
The aim of this project to identify the cellular targets of PMF that drive cancer chemoprevention. To achieve this a tagged version of PMF will be generated to pull out and identify proteins from cells that bind to this compound. This is a proof-of concept project to be repeated in the future with other plant extract-derived compounds in Malaysia that target cancer and other non-communicable diseases.

Project Outline
This project is part of the University of Kent’s Global Challenges Doctoral Centre (GCDC), established to enable UK researchers to collaborate with those in LMICs to address their development needs. As well as the primary scientific project, the student will receive interdisciplinary GCDC training, and undertake trips to Malaysia to work with collaborators.

Objectives
- Tag PMF with biotin and covalent modifiers in various positions through chemical synthesis, and then use cellular assays to identify which has the activity most similar to PMF itself.

- Perform pull-down studies on the lysates of precancerous and cancer colon cells to separate the proteins bound by PMF. The proteins will then be identified by mass spectrometry.

- Cellular studies to determine whether loss of function of each protein target in cells recapitulates the PMF cancer chemoprevention phenotype.

Supervisors
This project will be jointly supervised by:
Prof Michelle Garrett (Kent Biosciences) who has a leading record in cancer therapeutics
Dr Christopher Serpell
(Kent Physical Sciences) who is an expert in chemical manipulation of biomolecules
Dr Isabel Fong Lim (Universiti Malaysia Sarawak), remotely, who is the global leader in PMF studies

They will provide a rich interdisciplinary research environment, and the student will be integrated into both the Garrett and Serpell groups, as well as making trips to Dr Fong in Malaysia for training.

Recent Relevant References
- IL Fong, PhD thesis (2011) University of Leicester. https://lra.le.ac.uk/handle/2381/10376
- Wright MH, Sieber SA.(2016) Chemical proteomics approaches for identifying the cellular targets of natural products. Nat Prod Rep. 33:681-708.
- M. S. Akkad, C. J. Serpell, Degradable Polymers and Nanoparticles Built from Salicylic Acid, Macromolecular Rapid Communications, 2018, 39, 1800182

Criteria

Person specification: 
The successful candidate is expected to be a highly motivated student with an interest in multidisciplinary research and global development challenges. 
  • He/she will be expected to have an undergraduate (BSc) degree at 2(i) or higher in Chemistry, or a related discipline, with experience in chemical synthesis.  
  • The successful candidate is expected to be a highly motivated student with an interest in multidisciplinary research and global development challenges. 
  • They will require the aptitude to learning cellular and molecular biology techniques. 
  • The candidate will have the access to a range of synthetic and analytical chemistry, protein biochemistry, and molecular and cell biology. 
  • This project will provide the candidate with a broad multidisciplinary scientific training.
  • Candidates applying for a PhD degree must normally hold a good Honours degree (First or 2:1) or a Master’s Degree (at Merit or Distinction) in a relevant, appropriate subject, or the equivalent from an internationally recognised institution 
  • The University of Kent requires all non-native speaker of English to reach a minimum standard of proficiency in written and spoken English before beginning a postgraduate degree. For more information on English language requirements, please visit this page.  
Informal enquiries can be addressed to Michelle Garrett (M.D.Garrett@kent.ac.uk) or Chris Serpell (C.J.Serpell@kent.ac.uk).

The scholarship call is open to applicants from all nationalities.
Applicants paying Overseas fees can still apply: some academic schools may be able to support applicants financially beyond the UKRI level.

How to apply

When applying, students should follow the University of Kent’s online application process.

As part of the process, students should include the following:
- specify the project they wish to apply for;
- explain reasons for study;
- provide details/evidence of qualifications;
- provide two academic references;
- provide other personal information and supporting documentation.

To apply please go to: https://www.kent.ac.uk/courses/postgraduate/18/chemistry.

You will need to apply through the online application form on the main University website. Please note that you will be expected to provide personal details, education and employment history and supporting documentation (Curriculum Vitae, transcript of results, two academic references). The title of this project can be used in the Proposal section. Applications must be received by Sunday 20th January 2019, and interviews will be held by Friday 8th February.

Deadline

Applications are now closed


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