Postgraduate research opportunities

Towards the development of a novel class of broad-spectrum anti-infective drugs

You will work under the supervision of Dr Fraser J. Scott to develop Strathclyde Minor Groove Binders as novel anti-infective agents. Experimental work may include organic chemistry, biochemistry (enzyme assays), biophysisl (UV-vis, NMR) and microbiology (in vitro activity).

Number of places

1

Opens

10 March 2021

Duration

3-4 years

Eligibility

Candidates will have some previous experience in either:

  • Chemical synthesis
  • Microbiology
  • Biochemistry
  • Biophysical techniques

UKRI Studentship Eligibility

The eligibility criteria for UKRI funding has changed for studentships commencing in the 2021/22 academic year. Now, all home and international students are eligible to apply for UKRI funding which will cover the full stipend and tuition fees at the home rate (not the international rate). Under the new criteria, UKRI have stipulated a maximum percentage of international students that can be recruited each year against individual training grants. This will be managed at the institutional level for all EPSRC DTP and ICASE grants. For EPSRC CDT grants, this will be managed by the individual CDT administrative/management team. For ESRC and AHRC studentships the final funding decision will be made by the respective grant holder.

 

To be classed as a home student, applicants must meet the following criteria:

  • Be a UK national (meeting residency requirements), or
  • Have settled status, or
  • Have pre-settled status (meeting residency requirements), or
  • Have indefinite leave to remain or enter.

 

The residency requirements are based on the Education (Fees and Awards) (England) Regulations 2007 and subsequent amendments. Normally to be eligible for a full award a student must have no restrictions on how long they can stay in the UK and have been ordinarily resident in the UK for at least 3 years prior to the start of the studentship (with some further constraint regarding residence for education).

If a student does not meet the criteria above, they will be classed as an international student. The international portion of the tuition fee cannot be funded by the UKRI grant and must be covered from other sources. International students are permitted to self-fund the difference between the home and international fee rates.

Project Details

Through exceptionally strong research collaborations at the interface of chemistry, biology, and medicine, we have applied innovative thinking to the field of (Minor Groove Binders) MGBs to develop a novel platform for drug discovery with the potential to treat an impressive range of diseases, including bacterial, fungal, parasitic, and viral infections. This platform, the Strathclyde Minor Groove Binders (S-MGBs) has evolved from the first discovered MGB, distamycin, and we can design novel compounds with tailored activities through a detailed understanding of DNA binding, sequence selectivity, and physicochemical characteristics.

 

MGB lead compounds have in vivo activity (MIC = 0.2 µg/mL) against Gram-positive bacteria. In December 2015 our commercial partner, MGB Biopharma, completed the successful Phase I Clinical Trial (NCT02518607) of our lead candidate MGB-BP-3 for the treatment of Clostridium difficile infections; it is now going through Phase IIa. MGB-BP-3 is taken up selectively by bacterial cells and interacts with bacterial DNA. Its mode of action is consistent with the arrest of transcription of a number of essential genes. Thus, the multi-target nature of binding of MGB-BP-3 may indicate why we have never seen mutation to resistance for this compound. Several bacterial resistance mechanisms would thus have to be developed at once for a new MGB drug to become ineffective. This indicates that MGBs are very suitable drugs for the AMR era because several new bacterial resistance mechanisms would thus have to evolve together for a new MGB drug to become ineffective.

 

Recently, researchers at the University of Strathclyde, including the Scott research group, have begun to significantly expand the therapeutic potential of the S-MGB drug discovery platform. 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;1 Human African Trypanosomiasis and Malaria with Griffith University;2 Tuberculosis with University of Cape Town;3 Cryptococus neoformas and Candida auris with University of Manchester;4 and a variety of cancers with the Universites of Huddersfield and Strathclyde.5

There remains much work that can be done in developing new generations of S-MGBs with improved activities, reduced toxicity, and pathogen specificity, in order to progress compounds to pre-clinical development and beyond.

Interested potential PhD candidates will have the opportunity to engage in our drug design programme, but will be able to choose the specific focus of the project that most interests them, in discussion with the PI. For example, projects might include a significant organic and medicinal chemistry component, or pathogen microbiology, and there will be the potential to gain skills in biochemical assays (such as enzyme inhibition), and biophysical studies (such as UV-vis and NMR).

Moreover, the specific target infectious organism is also up for discussion.

Funding Details

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

Students applying should have (or expect to achieve) a minimum 2.1 undergraduate degree in a relevant science discipline. Candidates with masters level are preferred, but exceptional candidates at bachelors level can also be considered.

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