Rowena E. Martin
Australian National University
ChloroquinePlasmodium falciparumBiochemistryBiologyPharmacology
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Publications 36
#1Rowena E. Martin (ANU: Australian National University)H-Index: 18
Membrane transport proteins, also known as transporters, control the movement of ions, nutrients, metabolites, and waste products across the membranes of a cell and are central to its biology. Proteins of this type also serve as drug targets and are key players in the phenomenon of drug resistance. The malaria parasite has a relatively reduced transportome, with only approximately 2.5% of its genes encoding transporters. Even so, assigning functions and physiological roles to these proteins, and...
#1Vicky Zhang (ANU: Australian National University)
#2Robert Kucharski (ANU: Australian National University)H-Index: 26
Last. Ryszard Maleszka (ANU: Australian National University)H-Index: 44
view all 7 authors...
Dopamine is an important neuromodulator involved in reward-processing, movement control, motivational responses, and other aspects of behaviour in most animals. In honey bees (Apis mellifera), the dopaminergic system has been implicated in an elaborate pheromonal communication network between individuals and in the differentiation of females into reproductive (queen) and sterile (worker) castes. Here we have identified and characterised a honey bee dopamine transporter (AmDAT) and a splice varia...
#1Rowena E. Martin (ANU: Australian National University)H-Index: 18
#2Sarah H. Shafik (ANU: Australian National University)H-Index: 7
Last. Sashika N. Richards (ANU: Australian National University)H-Index: 4
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The deployment of artemisinin-based combination therapies (ACTs) has been, and continues to be, integral to reducing the number of malaria cases and deaths. However, their efficacy is being increasingly jeopardized by the emergence and spread of parasites that are resistant (or partially resistant) to the artemisinin derivatives and to their partner drugs, with the efficacy of the latter being especially crucial for treatment success. A detailed understanding of the genetic determinants of resis...
5 CitationsSource
#1Ellen Bushell (Wellcome Trust Sanger Institute)H-Index: 11
#2Ana R. Gomes (Wellcome Trust Sanger Institute)H-Index: 26
Last. Oliver Billker (Wellcome Trust Sanger Institute)H-Index: 39
view all 18 authors...
The genomes of malaria parasites contain many genes of unknown function. To assist drug development through the identification of essential genes and pathways, we have measured competitive growth rates in mice of 2,578 barcoded Plasmodium berghei knockout mutants, representing >50% of the genome, and created a phenotype database. At a single stage of its complex life cycle, P. berghei requires two-thirds of genes for optimal growth, the highest proportion reported from any organism and a probabl...
120 CitationsSource
#2Simon A. CobboldH-Index: 11
Last. Adele M. LehaneH-Index: 17
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13 CitationsSource
#1Sashika N. Richards (ANU: Australian National University)H-Index: 4
#2Megan N. Nash (ANU: Australian National University)H-Index: 5
Last. Rowena E. Martin (ANU: Australian National University)H-Index: 18
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Mutations in the Plasmodium falciparum ‘chloroquine resistance transporter’ (PfCRT) confer resistance to chloroquine (CQ) and related antimalarials by enabling the protein to transport these drugs away from their targets within the parasite’s digestive vacuole (DV). However, CQ resistance-conferring isoforms of PfCRT (PfCRTCQR) also render the parasite hypersensitive to a subset of structurally-diverse pharmacons. Moreover, mutations in PfCRTCQR that suppress the parasite’s hypersensitivity to t...
11 CitationsSource
#1M. Isabel Veiga (RMIT: RMIT University)H-Index: 6
#2Satish K. Dhingra (CUMC: Columbia University Medical Center)H-Index: 6
Last. David A. Fidock (CUMC: Columbia University Medical Center)H-Index: 65
view all 9 authors...
Antimalarial chemotherapy, globally reliant on artemisinin-based combination therapies (ACTs), is threatened by the spread of drug resistance in Plasmodium falciparum parasites. Here we use zinc-finger nucleases to genetically modify the multidrug resistance-1 transporter PfMDR1 at amino acids 86 and 184, and demonstrate that the widely prevalent N86Y mutation augments resistance to the ACT partner drug amodiaquine and the former first-line agent chloroquine. In contrast, N86Y increases parasite...
61 CitationsSource
#1Donelly A. van Schalkwyk (ANU: Australian National University)H-Index: 14
#2Megan N. Nash (ANU: Australian National University)H-Index: 5
Last. Rowena E. Martin (ANU: Australian National University)H-Index: 18
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It is becoming increasingly apparent that certain mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) alter the parasite's susceptibility to diverse compounds. Here we investigated the interaction of PfCRT with 3 tricyclic compounds that have been used to treat malaria (quinacrine [QC] and methylene blue [MB]) or to study P. falciparum (acridine orange [AO]). We measured the antiplasmodial activities of QC, MB, and AO against chloroquine-resistant and chloroquine-se...
11 CitationsSource
#1Serena Pulcini (Lond: University of London)H-Index: 4
#2Henry M. Staines (Lond: University of London)H-Index: 24
Last. Sanjeev Krishna S (Lond: University of London)H-Index: 57
view all 17 authors...
Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, are the major determinant of chloroquine resistance in this lethal human malaria parasite. Here, we describe P. falciparum lines subjected to selection by amantadine or blasticidin that carry PfCRT mutations (C101F or L272F), causing the development of enlarged food vacuoles. These parasites also have increased sensitivity to chloroquine and some other quinoline antimalarials, but exhibit no or minimal change in se...
22 CitationsSource
#1Rosa V. Marchetti (ANU: Australian National University)H-Index: 5
#2Adele M. Lehane (ANU: Australian National University)H-Index: 17
Last. Kiaran Kirk (ANU: Australian National University)H-Index: 44
view all 6 authors...
This work was supported by grants from the Australian National Health and Medical Research Council (NHMRC; 316933 and 525428 to K.K. and 1007035 to R.E.M.), and by the L’Ore´al Australia For Women in Science programme (R.E.M.). A.M.L. was supported by an NHMRC Overseas Biomedical Fellowship (585519) and R.E.M. was supported by NHMRC Australian Biomedical Fellowships (520320 and 1053082).
23 CitationsSource