We are very proud to share that our group’s first collaboration with the Drug Discovery Unit is now published in Science Translational Medicine, on the STM website HERE. To download an open-access copy you can use the link on the Drug Discovery Unit’s publication website HERE.
“Cryptosporidium lysyl-tRNA synthetase inhibitors define the interplay between solubility and permeability required to achieve efficacy”
Caldwell N, Peet C, Miller P, Colon BL, Taylor MG, Cocco M, Dawson A, Lukac I, Teixeira JE, Robinson L, Frame L, Seizova S, Damerow S, Tamaki F, Post J, Riley J, Mutter N, Hanna JC, Ferguson L, Hu X, Tinti M, Forte B, Norcross NR, Campbell PS, Svensen N, Caldwell FC, Jansen C, Postis V, Read KD*, Huston CD*, Gilbert IH*, Baragaña B*, Pawlowic MC*. Cryptosporidium lysyl-tRNA synthetase inhibitors define the interplay between solubility and permeability required to achieve efficacy. Sci Transl Med. 2024 Oct 23;16(770):eadm8631. doi: 10.1126/scitranslmed.adm8631. Epub 2024 Oct 23. PMID: 39441903.
This was done in collaboration with the Drug Discovery Unit and Chris Huston’s lab at the University of Vermont. It was a pleasure to work with Nicola on writing the paper and has been an incredible learning experience for myself and the lab. Thanks to Ian, Beatriz, Chris, Kev, and all the members of the DDU. I really appreciate the teamwork and opportunity to collaborate on this exciting project, funded in part by UKRI-MRC.
Authors from the Pawlowic lab underlined above. Beatrice Colon, our first postdoc, worked very hard to establish both acute and chronic infection models early on in the lab. When Lee joined the group, they worked together to adopt these specifically as efficacy models to test new therapeutics. Simona, Beatrice, Lee, and Flora set up the chronic efficacy study. Beatrice and Lee coordinated and performed the qPCR for the cow samples (600 fecal samples from calves!). Jack performed in vitro assays on the two late leads with his CpKRS mutants and confirmed that they’re still on target (read about it HERE). He also performed quantitative proteomics on his strain that overexpresses CpKRS with analysis help from Michele Tinti.
We are really excited to share the data and outstanding performance of these two late-lead molecules in all in vivo models, including calves.
The publication has been featured by many other groups, read their synopsis here:
Moredun Research Institute website: https://moredun.org.uk/news/moredun-scientific/university-of-dundee-and-moredun-scientific-a-step-in-the-right-direction-for-treatment-of-cryptosporidiosis
Farmers’ Weekly: https://www.fwi.co.uk/livestock/youngstock-management/two-drugs-impress-in-calf-cryptosporidiosis-trial?utm_source=homelatestnews
Chemical and Engineering News, Infection: https://cen.acs.org/biological-chemistry/infectious-disease/Two-compounds-reduce-Cryptosporidium-parasites-mice-and-calves/102/i34
Scottish Farmer: https://www.thescottishfarmer.co.uk/news/24683597.step-right-direction-treatment-cryptosporidiosis/
Control of Worms Sustainably (COWS): https://www.cattleparasites.org.uk/a-step-in-there-right-direction-for-treatment-of-cryptosporidosis/
Over the Counter: https://www.overthecounter.news/university-of-dundee-and-moredun-scientific-a-step-in-the-right-direction-for-treatment-of-cryptosporidiosis/
Fierce Biotech: https://www.fiercebiotech.com/research/two-new-drugs-reduce-cryptosporidiosis-parasite-numbers-infected-mice-and-calves
Mattie Christine Pawlowic Lab 