Genetic manipulation of Cryptosporidium parasites

Cryptosporidiosis is a disease that affects both humans and cattle. Specifically, C. parvum is zoonotic and can be transmitted between human and cattle. In humans, cryptosporidiosis causes diarrheal disease which can be severe and even fatal for the immunocompromised and for malnourished children.

In cattle, scouring is often caused by cryptosporidiosis, which can result in death or weight loss. This impact of animal health leads to economic loss affecting farmers both in low, middle, and high-income countries, including the UK. Unfortunately, the only drug approved to treat cryptosporidiosis in patients in ineffective in the patient populations that are at the highest risk of severe disease, and the treatment available for cattle has issues regarding toxicity.

There is no vaccine to prevent infection with Cryptosporidium, and due to the nature of transmissions, it is very difficult to remove Cryptosporidium from the environment. A OneHealth approach is required to tackle this important pathogen (PMID: 31983609).

The Pawlowic lab uses genetics and biochemical approaches to investigate the biology of this important pathogen. We also collaborate with drug discovery scientists to test new medicines and to decipher the mode of action for these new drugs. We recently published our work to develop new technology for target identification of anti-cryptosporidial compounds and use genetics to validate lysyl-tRNA synthetase as a drug target (PMID: 37600947).

In this publication we also develop a second selection marker, expanding the range of genetic tools available for Cryptosporidium.

In this PhD project, we will use genetics and biochemical approaches to investigate parasite biology. PhD students will gain experience in designing CRISPR, animal work, cell culture, molecular biology, microscopy, and proteomics. There will be opportunities to work with our collaborators in the Mode-of-Action group and the Drug Discovery Unit.

The Pawlowic Lab values honesty, collaborativeness, trustworthiness, dedication, and enthusiasm. Members of the lab are expected to uphold and practice these values, adhere to a high standard of research ethics, and contribute to a positive research culture