Personal profile

Research interests

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.

3. Mitochondrial function in the amitochondrial human pathogens Entamoeba histolytica and Giardia intestinalis

 

Mitochondrial acquisition is regarded as one of the most significant events in the evolution of the eukaryotic lineage. Given the relevance of the mitochondrion in the biology and evolution of extant eukaryotes, we are investigating the role and evolution of mitochondrial function in organisms that once harboured the organelle but have since lost many mitochondrial functions secondarily. We are particularly interested in two such organisms, Entamoeba histolytica and Giardia intestinalis, because of their high impact on human health and their socio-economic importance.

We have reported the existence of relict mitochondrial organelles - generically known as mitosomes - in Giardia and Entamoeba. We use ultra-structural studies and characterisation of their enzymatic and structural components using biochemical, gene cloning, and immunodetection methodologies to advance our understanding of the evolution of relict mitochondrial organelles in amitochondriate organisms.

 

 
 

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being