A collaboration between the research laboratories of Dr Mattie Pawlowic and Dr Susan Wyllie in the Wellcome Centre for Anti-Infectives Research has generated a new tool that can be used for studying Cryptosporidium.
This will aid scientists in the development of potential new medicines for a disease which currently has few treatment options. This work has been published in Frontiers in Cellular and Infection Microbiology.
Cryptosporidiosis causes devastating diarrheal disease in immunocompromised adults and malnourished children. Unfortunately, there is no vaccine or effective treatment. Several groups have been working to create new medicines for Cryptosporidiosis, including the Drug Discovery Unit at Dundee. There are a handful of compounds in pre-clinical development but currently there is a lack understanding for how most of them work to kill Cryptosporidium parasites. The Pawlowic Lab collaborates with Susan Wyllie’s Mode-of-Action lab to try and answer just that.
Dr Mattie Pawlowic, Principal Investigator and co-corresponding author of the study, said “We have adapted technologies to understand the mode of action of these anti-cryptosporidial compounds. Jack Hanna, a recently graduated PhD student from my lab, led the effort to develop proteomics-based and genetic based approaches for mode of action studies in Cryptosporidium.”
The genetic investigations led to the generation of a new tool that can be used to study Cryptosporidium. Previously, it was only possible to make a single genetic modification in the genome of Cryptosporidium. The technology developed in this study created a second “selection marker” that will allow two genetic modifications to be made.
Mattie continued, “This may not sound like much, but having only a single drug marker has really limited the kind of experiments we can conduct. A second selection marker will allow us to use more sophisticated genetic approaches and help us discover even more about this important parasite.”
The new tool will be able to be used to understand how other anti-cryptosporidial medicines in development work. This will help scientists advance those compounds closer to clinical development.
“This research was a true team effort over a number of years. First author Jack Hanna, Victor Corpas-Lopez (Postdoc in the Wyllie Lab), Simona Seizova (joint Postdoc in the Pawlowic and Wyllie Labs), Beatriz Baragana (from the DDU), and lots of people in the Pawlowic Lab (Beatrice Colon, Ross Bacchetti, Grant Hall, Emma Sands, Lee Robinson). I thank them and the specialist facility staff all for their vital contributions,” concluded Mattie.
The research was funded by the Medical Research Council, Wellcome Trust, Royal Society and the Carnegie Trust.