Developing novel treatments for invasive fungal infections

About the Project

Invasive Fungal Infections

Invasive fungal infections, such as those caused by the fungi Candida, are an increasing global public health concern. Those with underlying health problems or a weakened immune system are most at risk. This underrecognized global health threat is compounded by the rapid emergence of antifungal resistance.¹ Despite this, only four classes of antifungal medicines are used in clinical practice, with few others under development. In recognition of this global crisis, the World Health Organisation recently released their fungal priority pathogen list, which included several Candida pathogens.

Strathclyde Minor Groove Binders (S-MGBs)

S-MGBs are a completely new class of potential anti-infective agent that are based upon the natural product, distamycin. S-MGBs have structural similarity to distamycin but they have a novel mode of action.²

S-MGBs have clinically significant in vivo activity against Gram-positive bacteria. In December 2015 our commercial partner, MGB Biopharma, completed the successful Phase I Clinical Trial of the lead candidate MGB-BP-3; it has now successfully completed Phase IIa.³ MGB-BP-3 is taken up selectively by bacterial cells and interacts with DNA. Its mode of action is consistent with binding at multiple sites of bacterial DNA, interfering with various DNA-centric biochemical pathways, such as inhibiting topoisomerases or arresting transcription of essential genes.⁴

In addition to our success in developing antibacterial S-MGBs, their potential has been expanded to other infectious organisms. Specifically, efforts have resulted in the selection of lead compounds for the treatment of: Animal African Trypanosomiasis with the University of Glasgow, the University of Edinburgh and GALVmed;⁵ Human African Trypanosomiasis and Malaria with Griffith University;⁶ Tuberculosis with University of Cape Town;⁷ and, several clinically important fungal infections with the University of Manchester⁸

Resilience to resistance has been demonstrated in vitro for antibacterial, antifungal, and antitrypanosomal applications and is a consequence of the fact that S-MGBs target several essential DNA-centric processes in the pathogen.⁹ Because S-MGBs have multiple specific molecular targets the evolution of resistance is greatly repressed.

A special property of S-MGBs is that we can control the physicochemical properties whilst maintaining the essential antiparasitic activity. In this way, medicines can be designed to be effective in the challenging rural environments in India. This, together with their intrinsic resilience to the development of resistance makes S-MGBs an especially significant compound class in the search for new antileishmanial drugs.

Training Environment

Using advanced hit compounds identified from preliminary studies, in collaboration with national and international partners, the prospective student will carry out a comprehensive and systematic drug discovery campaign to identify new lead compounds for invasive fungal infections. This will involve routine and complex synthesis techniques, compound characterization using NMR, Mass Spec etc., and also target engagement studies using biophysical techniques. There may also be the opportunity to carryout in vitro biological evaluation of these compounds against fungal spp. in the labs of our various collaborators.

This project will suit a student with a background in synthetic organic chemistry or medicinal chemistry. Although it could be tailored to those wishing to pursue a biologically-focused project.

In addition to undertaking cutting edge research, students are also registered for the Postgraduate Certificate in Researcher Development (PGCert), which is a supplementary qualification that develops a student’s skills, networks and career prospects.

How To Apply

An upper second-class UK Honours degree or overseas equivalent in a relevant discipline is required. If English is not your first language, you must have an IELTS score of at least 6.5 with no component below 5.5

Interested candidates should email Dr Fraser Scott in the first instance.

Funding Notes

This project is suitable for self-funded candidates only. This may be through a personal scholarship that has already been secured or for an identified scholarship that a candidate would like to apply for with the supervisor.