Using complex glycans as drug delivery vectors

The development of small molecules to treat human disease and enhance quality of life, is one of the most important areas in biotechnology. There are several key aspects of small molecules which need to be considered, including; (i) the efficacy against their target, (ii) establishing what the off target effects are, and (iii) determining how the molecule should best be delivered. Both efficacy and off-target effects can be optimised through effective, targeted, drug delivery. For instance, the ability to target a drug to a specific, localised area, will increase its effective concentration thus reducing off-target effects.

The colonic environment is one area where drug targeting would be of great benefit in treating such debilitating, localised diseases as ulcerative colitis, Crohn’s disease, irritable bowel syndrome, chronic pancreatitis and colon cancer. Furthermore, the colon could also be exploited as a site for systemic absorption to treat non-colonic conditions. There are, however, a number of challenges facing colonic drug delivery. The colon is at the distal part of the gastrointestinal (GI) tract and drugs must travel its full length in order to reach the target site. There are drastic changes in pH from the gastric environment to the colonic environment and the drug must survive both. The presence of food, metabolic enzymes and a vast microbial community, especially in the colon, further add to the complexity of the system.

Complex glycans (GAGs) already make it to the colon intact and the bacteria in the colon have the required enzymatic apparatus to metabolise them. This makes GAGs an ideal potential mechanism for colonic drug delivery. Two key parameters are needed to utilise GAGs for drug delivery: knowledge of the glycan’s composition and structure and detailed molecular insights into the proteins that metabolise them. It is with these key parameters in mind that the focus of this proposal will be to develop glycans for potential drug delivery. Furthermore, GAGs have been shown to be high priority substrates for gut bacteria. This means their metabolism is not repressed, or altered, by the presence of other glycans, including glucose. This is ideal for a drug delivery system as the GAG vehicle will be resistant to sudden dietary changes. This PhD will provide the student with unique multidisciplinary training in chemistry, biochemistry and high-resolution microscopy providing them with a wide breadth of skills that will render them highly employable to both the industry and academia.

HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project and at the selected University. Applications not meeting these criteria will be rejected.

In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to [Email Address Removed]

The closing date for applications is Monday 18th May at 12noon.