This PhD in medicinal chemistry is designed to identify novel inhibitors of the pro-survival protein Mcl-1. The ability to evade cell death/apoptosis is a hallmark of cancer and there are vast arrays of cellular mechanisms in place which tumour cells employ to achieve this.1 One such example is Mcl-1, a member of a larger family of proteins called the Bcl-2 family. This family of proteins contains around 20 members and is responsible for controlling the apoptosis pathway.2 There are both pro- and anti-apoptotic proteins which in a healthy cell are carefully balanced to control its fate. However, in cancer high levels of the anti-apoptotic (pro-survival) proteins are often observed and not only contribute to the development of the tumour but also confer resistance to current therapies including chemotherapy and radiation treatment. In particular, elevated levels of Mcl-1 are one of the most commonly observed abnormalities in human cancer3 and are associated with the observed resistance to current therapies4,5. This PhD seeks to address this problem and identify novel small molecule inhibitors of Mcl-1. It will involve solid phase peptide synthesis as well as the biophysical and biological evaluation of the peptides synthesised.
This project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at http://www.uea.ac.uk/pgresearch/pgrfees.
A bench fee is also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. The amount charged annually will vary considerably depending on the nature of the project and applicants should contact the primary supervisor for further information about the fee associated with the project.
1) Hanahan D, Weinber RA, Cell, 2011, 144, 646
2) Juin P, Geneste O et al, Nat. Rev. Cancer, 2013 13, 455
3) Beroukhim R, Mermel CH et al, Nature, 2010, 463, 899. (
4) Wei S-H, Dong K et al, Cancer Chemother. Pharmacol., 2008, 62, 1055
5) Wertz IE, Kusam S et al, Nature, 2011, 471, 110