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Genetics and Development

Infections and Immunity

Neurosciences

Structural Biology

Delmiro Fernandez-Reyes group

Proteome-wide host-parasite interactions of severe malaria infections

Human malaria caused by Plasmodium falciparum represents a global disease burden with an estimated 500 million clinical episodes per year. Cerebral malaria and severe malarial anaemia are major complications with significant mortality and morbidity. Our research focuses on understanding how the proteomes of host and parasite interact to establish severe disease states. Proteome-wide profiling of the infectious process provides us with disease-specific molecular fingerprints reflecting host-pathogen interactions.

We study the parasite–host interactions using high-throughput proteome-wide mass spectrometry that reveals a snapshot of the state of the host during infection. We develop computational statistics and systems biology algorithms to discover complex patterns of interactions. Subsequent study of the patterns is essential for understanding the pathogenesis of different severe malaria clinical presentations and provides information for development of new diagnostic tests and therapeutic strategies. The establishment of the Childhood Malaria Research Unit with our collaborators at the Department of Paediatrics of the University College Hospital Ibadan, Nigeria allows us to sample the malaria disease process. This involves recruiting severe and non-severe malaria cases, as well as associated clinical, epidemiological, demographical and geographical information.

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(a) Plasma proteome-wide profiles of host-parasite interactions in patients with Severe Malaria Anaemia (Red), Cerebral Malaria (Purple), Uncomplicated Malaria (Orange). (b) Principal components analysis of complex patterns within plasma proteome profiles shows discrimination between clinical classes.

The Childhood Malaria Research Group (CMRG) based at University College Hospital (UCH Ibadan-Nigeria) has been established as a partnership between NIMR and the Department of Paediatrics of the College of Medicine University of Ibadan.

Selected publications

Rojas-Galeano, S; Hsieh, E; Agranoff, D; Krishna, S and Fernandez-Reyes, D (2008)
Estimation of relevant variables on high-dimensional biological patterns using iterated weighted kernel functions.
PLoS ONE 3, e1806 PubMed abstract
Agranoff, D; Fernandez-Reyes, D; Papadopoulos, MC; Rojas, SA; Herbster, M; Loosemore, A; Tarelli, E; Sheldon, J; Schwenk, A; Pollak, R; Rayner, CFJ and Krishna, S (2006)
Identification of diagnostic markers for tuberculosis by proteomic fingerprinting of serum.
Lancet 368, 1012-1021 PubMed abstract
Rojas, SA and Fernandez-Reyes, D (2005)
Adapting multiple kernel parameters for support vector machines using genetic algorithms.
2005 IEEE Congress on Evolutionary Computation, Proceedings: Edinburgh 1, 626-631