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Professor David Baker

BSc PhD

Professor
of Malaria Parasite Biology

Room
Room 314b

LSHTM
Keppel Street
London
WC1E 7HT
United Kingdom

Tel.
+44 (0) 20 7927 2664

David completed his PhD in 1988 at the University of Hull on the molecular biology of the intestinal parasite Giardia lamblia. He then moved to the London School of Hygiene & Tropical Medicine to work on the sexual stages of the malaria parasite Plasmodium falciparum. Current research is focused on investigating signal transduction pathways that regulate development of the most serious human malaria parasite Plasmodium falciparum. David is also involved in drug discovery work to exploit knowledge generated on these pathways to develop new antimalarial drugs.

Affiliations

Faculty of Infectious and Tropical Diseases
Department of Pathogen Molecular Biology

Centres

Malaria Centre

Teaching

I am involved in various aspects of teaching the MSc in Molecular Biology of Infectious Diseases (MBID). I organise the D2 Module - Molecular Biology: Research Progress and Applications (3160).

 

Research

David Baker’s research group uses biochemical and genetic approaches to study the cyclic nucleotide signal transduction pathways of malaria parasites. The cyclic nucleotides cAMP and cGMP perform a whole spectrum of cellular functions in diverse organisms. Earlier work from other laboratories suggested that both of these second messenger molecules may play roles in malaria parasite differentiation. David's studies have focused on the cyclase enzymes that synthesise cyclic nucleotides, the phosphodiesterases that degrade them, but also on the protein kinase that is activated by cGMP (PKG). David's group have found that in Plasmodium falciparum cGMP and PKG play an essential role in triggering the activation of mature sexual parasite forms (gametocytes) which are required to transmit disease to the mosquito vector. As part of a collaboration they also showed that this pathway is important for the development and motility of the ookinete form of P. berghei within the mosquito. It is now becoming clear that cGMP signalling and the PKG enzyme are vital for multiple parasite stages, because using specific PKG inhibitors in conjunction with inhibitor-insensitive transgenic parasites David's team have demonstrated that asexual blood stage schizogony cannot progress if this kinase is blocked. With others they have shown that PKG functions upstream of a protease cascade and a calcium-dependent protein kinase (CDPK5) also required for asexual blood stage schizont rupture and merozoite egress. More recently, through another collaboration, they showed that PKG activity stimulates calcium release required for merozoite egress and that this is likely mediated through regulation of phosphoinositide metablism. Since drug resistance is a huge problem, David's group are investigating whether cyclic nucleotide signalling pathways could be targeted in the development of novel antimalarial drugs. 

David received a Wellcome Trust Senior Investigator Award in 2015. This is a joint award with Professor Mike Blackman at the Francis Crick Institute that will focus on the cGMP signalling pathway in malaria parasites.

 

 
Research Area
Drug discovery and development
Parasites
Pharmacokinetics
Protozoa
Discipline
Genomics
Biochemistry
Cell biology
Molecular biology
Parasitology
Disease and Health Conditions
Infectious disease
Malaria

Selected Publications

Plasmodium falciparum CRK4 directs continuous rounds of DNA replication during schizogony.
Ganter, M. ; Goldberg, J.M. ; Dvorin, J.D. ; Paulo, J.A. ; King, J.G. ; Tripathi, A.K. ; Paul, A.S. ; Yang, J. ; Coppens, I. ; Jiang, R.H. ; Elsworth, B. ; Baker, D.A. ; Dinglasan, R.R. ; Gygi, S.P. ; Duraisingh, M.T. ;
Nat Microbiol
Crystal Structures of the Carboxyl cGMP Binding Domain of the Plasmodium falciparum cGMP-dependent Protein Kinase Reveal a Novel Capping Triad Crucial for Merozoite Egress.
Kim, J.J. ; Flueck, C. ; Franz, E. ; Sanabria-Figueroa, E. ; Thompson, E. ; Lorenz, R. ; Bertinetti, D. ; Baker, D.A. ; Herberg, F.W. ; Kim, C. ;
PLoS Pathog
cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.
Ramdani, G. ; Naissant, B. ; Thompson, E. ; Breil, F. ; Lorthiois, A. ; Dupuy, F. ; Cummings, R. ; Duffier, Y. ; Corbett, Y. ; Mercereau-Puijalon, O. ; Vernick, K. ; Taramelli, D. ; Baker, D.A. ; Langsley, G. ; Lavazec, C. ;
PLoS Pathog
Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion.
Alam, M.M. ; Solyakov, L. ; Bottrill, A.R. ; Flueck, C. ; Siddiqui, F.A. ; Singh, S. ; Mistry, S. ; Viskaduraki, M. ; Lee, K. ; Hopp, C.S. ; Chitnis, C.E. ; Doerig, C. ; Moon, R.W. ; Green, J.L. ; Holder, A.A. ; Baker, D.A. ; Tobin, A.B. ;
Nat Commun
A transcriptional switch underlies commitment tosexual development in malaria parasites
Kafsack, B.F.; Rovira-Graells, N.; Clark, T.G.; Bancells, C.; Crowley, V.M.; Campino, S.G.; Williams, A.E.; Drought, L.G.; Kwiatkowski, D.P.; Baker, D.A.; Cortés, A.; Llinás, M.;
Nature
Phosphoinositide Metabolism Links cGMP-Dependent Protein Kinase G to Essential Ca2+ Signals at Key Decision Points in the Life Cycle of Malaria Parasites.
Brochet, M. ; Collins, M.O. ; Smith, T.K. ; Thompson, E. ; Sebastian, S. ; Volkmann, K. ; Schwach, F. ; Chappell, L. ; Gomes, A.R. ; Berriman, M. ; Rayner, J.C. ; Baker, D.A. ; Choudhary, J. ; Billker, O. ;
PLoS Biol
A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes.
Dvorin, J.D.; Martyn, D.C.; Patel, S.D.; Grimley, J.S.; Collins, C.R.; Hopp, C.S.; Bright, A.T.; Westenberger, S.; Winzeler, E.; Blackman, M.J.; Baker, D.A.; Wandless, T.J.; Duraisingh, M.T.;
Science
Gametogenesis in Malaria Parasites Is Mediated by the cGMP-Dependent Protein Kinase.
McRobert, L.; Taylor, C.J.; Deng, W.; Fivelman, Q.L.; Cummings, R.M.; Polley, S.D.; Billker, O.; Baker, D.A.;
PLoS Biol
See all Professor David Baker's Publications