Roles of pro-inflammatory and anti-inflammatory cytokines in causing cerebral complications in malaria

Summary

The balance of production of pro-inflammatory and anti-inflammatory cytokines seems to be critical in determining the outcomes of malaria infection and this will be studied in the context of cerebral malaria, a major life-threatening complication in this infection.

Supervisor(s)

Professor Nicholas Hunt

Research Location

Camperdown - School of Medical Sciences - Bosch Institute

Program Type

Masters/PHD

Synopsis

There are over 500 million malaria infections every year worldwide and these result in between 1 and 3 million deaths annually. Most victims are young children in Africa, pregnant women or visitors to malaria-endemic regions of the world. As well as causing great morbidity and mortality, malaria also adversely affects the economic and social fabric of those countries where it is a problem. Around 40% of the world’s population live in areas where malaria is endemic.The three complications of malaria that are particularly life-threatening are cerebral malaria (i.e. involvement of the brain), lung involvement and anaemia (loss of red blood cells). In our laboratory we work on the first two of these. This project is about the pathogenesis of cerebral malaria. We recently have shown (Mitchell A et al, Infection and Immunity 73, 5645-5653, 2005) that early production of immunomodulatory cytokines in the spleen seems to be protective against development of severe brain complications. This research project is part of a team approach to expanding this finding and describing the fine mechanisms that underlie the regulation of immunity to malaria and immunopathology caused by a dysregulated immune response. Components of the project include: 

• Work with an in vivo model of the disease
• Studies with isolated spleen cells in culture, looking at their pattern of production of immunomodulators including cytokines
• Co-culture studies where human cells are incubated together to re-create the lesions that occur in the small vessels of the brain in cerebral malaria.

This project is carried out in collaboration with the laboratories of Professor Georges Grau and Roland Stocker within the Medical Foundation Building.

Additional Information

Approaches: immunology, haematology, pathology, physiology, biochemistry, cell biology, molecular biology, disease models. Techniques: histopathology, cell culture, flow cytometry, co-culture studies, quantitative RT-PCR, gene expression techniques, microscopy. Other Information: Nick Hunt’s laboratory is in the newly-refurbished Medical Foundation Building. The equipment and other facilities in the building are first class, as are the other research groups located there. His research group contains 3 postdoctoral fellows, 2 PhD students and a part-time technician. The laboratory is well-funded by two National Health and Medical Research Council, one Australian Research Council and one Sir Zelman Cowen Foundation grant in 2009. Scholarships: Laboratory-funded scholarships may be available for suitably-qualified candidates.

Keywords

malaria, severe malaria, cerebral malaria, inflammatory disease, Infectious Disease, Endothelium, cytokines, immunopathology, gene expression, Immunology, immunity, blood vessels, Brain & nervous system disorders, Infectious diseases, Infection & immunity, Neuroscience & psychology

Opportunity ID

The opportunity ID for this research opportunity is: 116

Other opportunities with Professor Nicholas Hunt

• Pathogenic mechanisms involved in bacterial meningitis
• Mechanism of action of some novel anti-malarial compounds
• The role of a newly discovered enzyme, indoleamine dioxygenase-2, in health and in disease