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MRC DiMeN Doctoral Training Partnership: Combating drug resistance with evolutionary biology


MRC DiMeN Doctoral Training Partnership

, Wednesday, January 27, 2021 Competition Funded PhD Project (Students Worldwide)
Newcastle United Kingdom Biochemistry Bioinformatics Epidemiology Genetics Microbiology Molecular Biology Parasitology Pharmacology Structural Biology

About the Project

Our mission:

If we don’t find an urgent effective solution to the problem of drug resistance, then in less than 30 years from now resistant pathogens is going to become the major cause of death and will be taking more human lives than diabetes and cancer together. Then, many of humanity’s old nightmares—such as tuberculosis, gonorrhoea, blood poisoning, which were largely forgotten in the Era of Antibiotics—will return in its improved and ferocious form in the Era of Resistance—return to take hundreds of millions of human lives. 

How can we solve this problem? When agriculture underwent a similar major crisis in the form of pesticide resistance in the 1970s, scientists and the public developed the philosophy of Integrated Pest Management (IPM), which forever changed our approach to pest control. Instead of trying to eradicate every single pest, IPM advocated approaching pests as an evolutionary problem and managing pests at an acceptably low level, thereby reducing pesticide use, cutting costs, and minimizing the risks of pesticide resistance. Here, we invite you to join our team to help create a similar fundamental shift in the way we approach the therapeutic treatment of infectious diseases. 

Our approach:

In our laboratory, we use clinical isolates of the human pathogen Staphylococcus aureus to devise radically new methods to attenuate, prevent or reverse the evolution of drug resistance. 

Our experimental system involves:

- advanced microfluidics to run evolution experiments and observe how pathogens evolve drug resistance in real time;

- time-resolved genome sequencing to visualize evolutionary paths to resistance and improve our ability to predict how resistance evolves;

- cryo-EM analysis of drug-resistant molecules to provide an understanding of resistance mechanisms;

- biochemistry to assess how drug-resistance mutations impact the activity of biological molecules;

S. aureus genetics to reveal how resistance evolves from “within”, driven by the unique interplay of genetic factors;

- 3D printing of models of drug-resistant biological molecules for a museum exhibit.

Objectives and outcomes: 

Recently, we found new pioneering strategies to attenuate and reverse the evolution of resistance. We invite you to work with us and test two of these novel strategies using so-called drug cycling, “drug holidays”, personalized drug choice, and simultaneous use of drugs with overlapping binding sites in bacterial proteins.

This work will help create a new culture of drug application that will drastically extend the life of widely prescribed clinical antibiotics and give a second life to drugs that were suspended due to rapid evolution of resistance.

General training:

We take pride in trying hard to be the best possible mentors, running our labs as talent hotbeds, which are built not on identifying talent but on constructing it, day by day. Through our mentorship, you will master successful work ethic, effective academic writing, and much more.   

Requirement:

No specialized training is required, besides basic training in biology, physics or chemistry. Yet it will help if you are a motivated human being with a curious mind and kind heart. 

More:

https://melnikovlab.com/phd-projects/

https://www.ncl.ac.uk/medical-sciences/people/profile/tracypalmer.html

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards

Further information on the programme and how to apply can be found on our website:

https://bit.ly/3lQXR8A 


Funding Notes

Studentships are funded by the Medical Research Council (MRC) for 3.5yrs. Funding will cover UK tuition fees and stipend only. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme. Please read additional guidance here: View Website
Studentships commence: 1st October 2021
Good luck!

References

1. Exploiting evolutionary trade-offs for post-treatment management of drug-resistant populations. Melnikov SV et.al. (2020) PNAS 117 (30) 17924-17931.
2. A membrane-depolarizing toxin substrate of the Staphylococcus aureus type VII secretion system mediates intraspecies competition. Ulhuq FR et.al. (2020) PNAS 117(34): 20836–20847.
3. Error-prone protein synthesis in parasites with the smallest eukaryotic genome Melnikov SV et.al. (2018) PNAS 115 (27), E6245-E6253.

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