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Professor David Baker

BSc PhD

Professor
of Malaria Parasite Biology

Room
Room 393

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

Department of Infection Biology
Faculty of Infectious and Tropical Diseases

Centres

Malaria Centre

Teaching

I am involved in various aspects of teaching the Medical Parasitology and Medical Microbiology Masters courses. I co-organise the D2 Module - Molecular Biology: Research Progress and Applications (3160). I am the Deputy Chair of the Exam Board for the Infectious Diseases Masters module (Distance Learning).

 

Research

David Baker’s research group uses biochemical and genetic approaches to study the cyclic nucleotide signal transduction pathways of malaria parasites. These pathways are centred on the intracellular messenger molecules cAMP and cGMP which perform a whole spectrum of cellular functions in diverse organisms. David's studies have focused on the cyclase enzymes that synthesise cyclic nucleotides, the phosphodiesterases that degrade them, but also on the protein kinases that are activated by cGMP (PKG) and cAMP (PKA). 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. It is now becoming clear that cGMP signalling and the PKG enzyme are vital for multiple parasite stages; for example using specific PKG inhibitors in conjunction with inhibitor-insensitive transgenic parasites, David's team in collaboration with Mike Blackman at the Francis Crick Institute, have demonstrated that asexual blood stage egress is blocked if PKG is inhibited or conditionally disrupted. This collaboration has also recently demonstrated an essential role of cAMP and PKA signalling for erythrocyte invasion by P. falciparum merozoites. Through collaboration with Mathieu Brochet at the University of Geneva, David has shown 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 is also investigating whether cyclic nucleotide signalling pathways could be targeted in the development of novel antimalarial drugs. This is funded primarily by a Wellcome Trust Innovator Award in partnership with Salvensis and the Medicines for Malaria Venture (MMV).

David received a Wellcome Trust Senior Investigator Award in 2015. This was a joint award with Professor Mike Blackman at the Francis Crick Institute that focused on the cGMP signalling pathway in malaria parasites. A second joint Investigator Award to David and Mike will start in mid-2021 and will focus on the downstream players of cAMP signalling in blood stage 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
Tropical diseases

Selected Publications

Ca2+ signals critical for egress and gametogenesis in malaria parasites depend on a multipass membrane protein that interacts with PKG.
Balestra AC; Koussis K; Klages N; Howell SA; Flynn HR; Bantscheff M; Pasquarello C; Perrin AJ; Brusini L; Arboit P
2021
Science advances
Antimalarial activity of primaquine operates via a two-step biochemical relay.
Camarda G; Jirawatcharadech P; Priestley RS; Saif A; March S; Wong MHL; Leung S; Miller AB; Baker DA; Alano P
2019
Nature Communications
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
Phosphodiesterase beta is the master regulator of cAMP signalling during malaria parasite invasion.
Flueck C; Drought LG; Jones A; Patel A; Perrin AJ; Walker EM; Nofal SD; Snijders AP; Blackman MJ; Baker DA
2019
PLoS Biology
Rapid and iterative genome editing in the malaria parasite Plasmodium knowlesi provides new tools for P. vivax research.
Mohring F; Hart MN; Rawlinson TA; Henrici R; Charleston JA; Diez Benavente E; Patel A; Hall J; Almond N; Campino S
2019
eLife
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
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
Plasmodium falciparum CRK4 directs continuous rounds of DNA replication during schizogony.
Ganter M; Goldberg JM; Dvorin JD; Paulo JA; King JG; Tripathi AK; Paul AS; Yang J; Coppens I; Jiang RH
2017
Nature microbiology
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 to sexual 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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