The pharmaceutical industry has identified a major gap in its portfolio. On the one hand, they are excellent at discovering small molecules that act via a lock and key type mechanism. On the other hand, some diseases are only treatable with biologics such as antibodies and proteins, with associated high costs and difficulties in administering them. The gap between these is filled by large cyclic molecules which behave like small molecule drugs in terms of administration, and behave like biologics in terms of therapeutic effects. However, pharmaceutical industry has no easy way to make such molecules in quantity, nor are there simple ways to modify them.
We have discovered a range of enzymes that allows us to make complex modified cyclic peptides which have high biological activity in a number of human disease states. This process takes a few days, as compared to chemical synthesis which would take months or years.
In this project you will take a hybrid approach to the production of such compounds, using chemical synthesis together with enzymes to create a range of cyclic modified peptides for testing against a number of disease targets. You will gain skills in peptide synthesis, molecular biology, biochemistry and compound separation and identification.
You will work in a supportive group composed of molecular and cell biologists and synthetic and natural product chemists. The research environment for the biological and chemical parts of the project are world class. The biological work will be carried out at the Institute of Medical Sciences, and the chemical work will be carried out at the Marine Biodiscovery Centre.
Applicants must hold, or expect to receive, a first or upper second class honours degree (or equivalent) in Chemistry, biochemistry, cell and molecular biology or pharmacy with knowledge of Organic chemistry. Desirable knowledge includes Spectroscopy, Microbiology and Molecular biology.
The other supervisor on this project is Dr W Houssen, Institute of Medical Sciences, University of Aberdeen.
There is no funding attached to this project, it is for self-funded students only.
1. “The mechanism of patellamide macrocyclization revealed by study of the Prochloron sp PatG macrocyclase domain”, Jesko Koehnke, Andrew Bent, Wael E. Houssen, David Zollman, Falk Morawitz, Sally Shirran, Jeremie Vendome, Ada F. Nneoyiegbe, Laurent Trembleau, Catherine H. Botting, Margaret C. M. Smith, Marcel Jaspars, & James H. Naismith, Nat. Struct. Mol. Biol. 2012, 19, 767
2. “The Cyanobactin Heterocyclase Enzyme: A Processive Adenylase That Operates with a Defined Order of Reaction” Jesko Koehnke, Andrew F. Bent, David Zollman, Kieran Smith, Wael E. Houssen, Xiaofeng Zhu, Greg Mann, Tomas Lebl, Richard Scharff, Sally Shirran, Catherine H. Botting, Marcel Jaspars, Ulrich Schwarz-Linek, and James H. Naismith, Angew Chem, 2013, 52, 13991
Formal applications can be completed online: http://www.abdn.ac.uk/postgraduate/apply. You should apply for PhD in Chemistry, to ensure that your application is passed to the correct College for processing. Please ensure that you quote the project title and supervisor on the application form.
Informal inquiries can be made to Professor M Jaspars, (email@example.com) with a copy of your curriculum vitae and cover letter. All general enquiries should be directed to the Graduate School Admissions Unit (firstname.lastname@example.org).