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  4 Year MRC PhD Programme: Interdisciplinary approach to identifying drug targets and their mode of action in Cryptosporidium


   School of Life Sciences

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  Dr M Pawlowic, Dr S Wylie  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

Cryptosporidium is a major source of diarrheal-caused morbidity and mortality in young children worldwide. Unfortunately, there is no vaccines and no drugs available to treat cryptosporidiosis. Recent adaption of CRISPR/Cas9 in Cryptosporidium and establishment of disease models provide a great opportunity for major advancements in drug discovery.

This project aims to 1) use genetic approaches to characterize potential drug targets and 2) to determine the mode of action of anti-cryptosporidial compounds. The trainee will have the unique opportunity to engage in drug discovery from both biological and chemical perspectives.


With Dr. Pawlowic, the trainee will use CRISPR/Cas9 to genetically engineer Cryptosporidium to validate drug targets. They will also advance the drug discovery pipeline by testing compounds in vitro and in vivo. The trainee with also work with Dr. Wyllie, leader of the Mode of Action team, to adapt current technologies (whole-genome sequencing and chemical proteomics approaches) to define the mode of action and/or specific molecular targets of anti-cryptosporidial compounds. In the course of these studies the student will work closely with the scientists within our Drug Discovery Unit (http://drugdiscovery.dundee.ac.uk), gaining invaluable experience of the drug discovery process. This project requires an interdisciplinary approach and creativity to find new approaches in the emerging field of Cryptosporidium research.




References

References:

Generating and Maintaining Transgenic Cryptosporidium parvum Parasites. Pawlowic MC, Vinayak S, Sateriale A, Brooks CF, Striepen B. Curr Protoc Microbiol. 2017 Aug 11;46:20B.2.1-20B.2.32. doi: 10.1002/cpmc.33. PubMed PMID: 28800157;

PubMed Central PMCID: PMC5556942.

Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum. Vinayak S, Pawlowic MC, Sateriale A, Brooks CF, Studstill CJ, Bar-Peled Y, Cipriano MJ, Striepen B. Nature. 2015 Jul 23;523(7561):477-80. doi: 10.1038/nature14651. Epub 2015 Jul 15.

The cellular thermal shift assay for evaluating drug target interactions in cells. Jafari R, Almqvist H, Axelsson H, Ignatushchenko M, Lundbäck T, Nordlund P, Martinez Molina D. Nat Protoc. 2014 9(9):2100-22. PMID: 25101824

Activation of Bicyclic Nitro-drugs by a Novel Nitroreductase (NTR2) in Leishmania. Wyllie S, Roberts AJ, Norval S, Patterson S, Foth BJ, Berriman M, Read KD, Fairlamb AH. PLoS Pathog. 12(11):e1005971. PMID: 27812217.

Where will I study?

 About the Project