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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 Infection 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

Phosphodiesterase beta is the master regulator of cAMP signalling during malaria parasite invasion
Blackman MJ; Flueck C; Drought LG; Jones A; Patel A; Perrin AJ; Walker EM; Nofal S; Snijders AP; Baker DA
2019
PLoS Biology
Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery.
Patel A; Perrin AJ; Flynn HR; Bisson C; Withers-Martinez C; Treeck M; Flueck C; Nicastro G; Martin SR; Ramos A
2019
PLoS biology
Structures of the cGMP-dependent protein kinase in malaria parasites reveal a unique structural relay mechanism for activation.
El Bakkouri M; Kouidmi I; Wernimont AK; Amani M; Hutchinson A; Loppnau P; Kim JJ; Flueck C; Walker JR; Seitova A
2019
Proceedings of the National Academy of Sciences of the United States of America
Epistasis studies reveal redundancy among calcium-dependent protein kinases in motility and invasion of malaria parasites.
Fang H; Gomes AR; Klages N; Pino P; Maco B; Walker EM; Zenonos ZA; Angrisano F; Baum J; Doerig C
2018
Nature communications
The Actinomyosin Motor Drives Malaria Parasite Red Blood Cell Invasion but Not Egress.
Perrin AJ; Collins CR; Russell MRG; Collinson LM; Baker DA; Blackman MJ
2018
mBio
A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission.
Baker DA; Stewart LB; Large JM; Bowyer PW; Ansell KH; Jiménez-Díaz MB; El Bakkouri M; Birchall K; Dechering KJ; Bouloc NS
2017
Nature communications
Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion.
Alam MM; Solyakov L; Bottrill AR; Flueck C; Siddiqui FA; Singh S; Mistry S; Viskaduraki M; Lee K; Hopp CS
2015
Nature communications
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 MO; Smith TK; Thompson E; Sebastian S; Volkmann K; Schwach F; Chappell L; Gomes AR; Berriman M
2014
PLoS biology
A transcriptional switch underlies commitment tosexual development in malaria parasites
Kafsack BFC; Rovira-Graells N; Clark TG; Bancells C; Crowley VM; Campino SG; Williams AE; Drought LG; Kwiatkowski DP; Baker DA
2014
Nature
A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes.
Dvorin JD; Martyn DC; Patel SD; Grimley JS; Collins CR; Hopp CS; Bright AT; Westenberger S; Winzeler E; Blackman MJ
2010
Science (New York, NY)
Gametogenesis in Malaria Parasites Is Mediated by the cGMP-Dependent Protein Kinase.
McRobert L; Taylor CJ; Deng W; Fivelman QL; Cummings RM; Polley SD; Billker O; Baker DA
2008
PLoS biology
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