Jorge Tovar-Torres

1. Nucleic acid diagnostic testing for fungal infections

Human fungal infections have emerged as one of the most pressing health problems in recent years. Endemic infections affect healthy immunocompetent individuals causing a range of diseases which generally resolve with chemotherapy but hospital-acquired nosocomial infections pose a serious threat to immunocompromised patients in hospital wards and intensive care units worldwide. Despite the availability of chemotherapy nosocomial infections frequently result in high mortality rates, often exceeding 50%. The development of timely and more efficient molecular diagnostic methods, along with the development of new drugs and anti-fungal vaccines, was recently identified as one of the most pressing needs in medical mycology research.

We are interested in developing and implementing simple nucleic acids diagnostic tests for a range of fungal infections, including both endemic and opportunistic. We use Candida, the causative agent of endemic and nosocomial candidosis, as a test organism. Combining fungal genome data mining with isothermal DNA amplification, we aim to develop simple diagnostic tools that are both amenable to automation and applicable at the point of care.

Current opportunities in this area:

http://www.findaphd.com/search/ProjectDetails.aspx?PJID=56763&LID=1359

2. Lipid signalling and its role in Giardia intestinalis differentiation

Giardia is an intestinal parasite of humans that causes diarrhoeal disease. One of the most important aspects of the biology of this parasite is its cyclical developmental transformation between an environmentally resistant infective cyst and a gut colonising trophozoite. Although much is known about the transitional steps of encystation at the cellular level the molecular circuitry that regulates this process remains obscure. The physiological conditions required for the completion of the Giardia life cycle have been replicated in the laboratory, making this organism a simple eukaryotic model for the study of cell differentiation. Conditions of high bile lipid concentration or cholesterol starvation induce the formation of cysts in culture suggesting that lipids and lipid signalling may play a role in Giardia differentiation.

We have reported the existence of two giardial genes encoding phosphoinositide-3-kinase (PI3K) homologues, genes likely to play a role in lipid signalling. Expression and inhibition studies suggested that giardial PI3K signalling controls both extracellularly-initiated signalling events and intracellular vesicular protein sorting, processes. In addition, gene homologues encoding putative PPIn-metabolising enzymes and PPIn-binding proteins that may act as effectors downstream of PI3K were also identified in the Giardia genome, further documenting the existence of PI3K signalling networks in this organism. Using biochemical and molecular biological methods we are currently investigating how the early stages of encystation are regulated in this intestinal parasite.