A5101422097- Malaria Research and Control
- Trypanosoma species research and implications
- Mosquito-borne diseases and control
- Complement system in diseases
- Advancements in Transdermal Drug Delivery
- Parasites and Host Interactions
- Viral Infections and Vectors
- Vector-Borne Animal Diseases
- Venomous Animal Envenomation and Studies
- Drug Transport and Resistance Mechanisms
- Research on Leishmaniasis Studies
- Cholinesterase and Neurodegenerative Diseases
- Phosphodiesterase function and regulation
- Organic and Inorganic Chemical Reactions
- Bee Products Chemical Analysis
- Virus-based gene therapy research
- Biomedical Research and Pathophysiology
- Surgical Sutures and Adhesives
- Orthopedic Surgery and Rehabilitation
- Cholesterol and Lipid Metabolism
- Neurological diseases and metabolism
- Peroxisome Proliferator-Activated Receptors
- Contact Dermatitis and Allergies
- Insect Resistance and Genetics
- Advanced Drug Delivery Systems
London School of Hygiene & Tropical Medicine
2015-2024
Cadila Pharmaceuticals (India)
2023
University College London
2013-2021
University of London
2013-2020
Eastman Dental Hospital
2017
University of Reading
2012-2013
Medway School of Pharmacy
2013
Mount Sinai Hospital
1977
Cyclic AMP (cAMP) is an important signalling molecule across evolution, but its role in malaria parasites poorly understood. We have investigated the of cAMP asexual blood stage development Plasmodium falciparum through conditional disruption adenylyl cyclase beta (ACβ) and downstream effector, cAMP-dependent protein kinase (PKA). show that both production activity PKA are critical for erythrocyte invasion, whilst key developmental steps precede invasion still take place absence signalling....
Tackling relapsing Plasmodium vivax and zoonotic knowlesi infections is critical to reducing malaria incidence mortality worldwide. Understanding the biology of these important related parasites was previously constrained by lack robust molecular genetic approaches. Here, we establish CRISPR-Cas9 genome editing in a culture-adapted P. strain define parameters for optimal homology-driven repair. We scalable protocol production repair templates PCR demonstrate flexibility system tagging...
We examine in detail the AP-2 adaptin complex from malaria parasite Plasmodium falciparum . In most studied organisms, is involved bringing material into cell outside, a process called endocytosis. Previous work shows that changes to μ subunit of can contribute drug resistance. Our experiments show essential for development blood but does not have any role clathrin-mediated This suggests specialized function has developed parasites, and this may be important understanding its impact on
Cyclic nucleotide signalling is a major regulator of malaria parasite differentiation. Phosphodiesterase (PDE) enzymes are known to control cyclic GMP (cGMP) levels in the parasite, but mechanisms by which AMP (cAMP) regulated remain enigmatic. Here, we demonstrate that Plasmodium falciparum phosphodiesterase β (PDEβ) hydrolyses both cAMP and cGMP essential for blood stage viability. Conditional gene disruption causes profound reduction invasion erythrocytes rapid death those merozoites...
The composition of topical and transdermal formulations is known to determine the rate extent drug delivery through skin. However, date, role excipients in these on skin actives has received little attention from scientists field. Monitoring absorption both vehicle may provide insights into mechanism by which promote permeation facilitate design effective safer products. Previously, we have investigated use quantitative Confocal Raman Spectroscopy (CRS) investigate an active skin, also...
Plasmodium knowlesi is a zoonotic malaria parasite in Southeast Asia that can cause severe and fatal humans.The main hosts are Macaques, but modern diagnostic tools reveal increasing numbers of human infections.After P. falciparum, the only other capable being maintained long term vitro culture with red blood cells (RBCs).Its closer ancestry to non-falciparum parasites, more balanced AT-content, larger merozoites higher transfection efficiencies, gives some key advantages over P.falciparum...
Guanylyl cyclases (GCs) synthesize cyclic GMP (cGMP) and, together with nucleotide phosphodiesterases, are responsible for regulating levels of this intracellular messenger which mediates myriad functions across eukaryotes. In malaria parasites (
1. Insulin-resistant states are commonly associated with a significantly higher risk of atherosclerosis. Insulin resistance has also been correlated enhanced very low-density lipoprotein (VLDL) production, which is exacerbated by increased intestinal lipid synthesis and insulin-stimulated de novo lipogenesis. Microsomal triglyceride transfer protein (MTP) catalyses the critical step in secretion VLDL chylomicrons. The purpose present study was to test hypothesis that chronic inhibition MTP...
In model organisms, type IV ATPases (P4-ATPases) require cell division control protein 50 (CDC50) chaperones for their phospholipid flipping activity. the malaria parasite Plasmodium falciparum, guanylyl cyclase alpha (GCα) is an integral membrane that essential release (egress) of merozoites from host erythrocytes. GCα unusual in it contains both a C-terminal domain and N-terminal P4-ATPase unknown function. We sought to investigate whether any three CDC50 orthologues (termed A, B, C)...
Peptide nanofibres (PNFs) have gained increasing interest as engineered biomaterials for drug delivery and tissue repair because of the versatility in design they offer through self-assembly amphiphilic peptide molecules. Their is governed by hydrophobic interactions hydrogen bonds between sequences able to form β-sheets. In this report, we describe PNFs using palmitoyl-peptide molecules containing two different cationic amino acid a description nanofiber physicochemical characteristics. The...
The insect baculovirus AcMNPV (Autographa californica multiple nuclear polyhedrosis virus) enters many mammalian cell lines, prompting its application as a general eukaryotic gene delivery agent, but the basis of entry is poorly understood. For adherent cells, we show that favoured by low pH and increasing available cell-surface area through transient release from substratum. Low also stimulated into cells grown in suspension which, optimally, could reach 90% transduced population. basic...
Abstract We previously reported that the Plasmodium falciparum putative serine/threonine protein phosphatase 7 (PP7) is a high confidence substrate of cAMP-dependent kinase (PKA). Here we explore function PP7 in asexual P. blood stage parasites. show conditional disruption leads to severe growth arrest. calcium-dependent which interacts with calmodulin and 1 (CDPK1), consistent role calcium signalling. Notably, was found be dispensable for erythrocyte invasion, but crucial ring-stage...
ABSTRACT We previously reported that the Plasmodium falciparum putative serine/threonine protein phosphatase 7 (PP7) is a high-confidence substrate of cAMP-dependent kinase (PKA). Here we explore function PP7 in asexual P. blood stage parasites. show conditional disruption leads to severe growth arrest. calcium-dependent interacts with calmodulin and 1 (CDPK1), consistent role calcium signaling. Notably, was found be dispensable for erythrocyte invasion, but crucial ring-stage development,...
Cyclic nucleotide–dependent phosphodiesterases (PDEs) play essential roles in regulating the malaria parasite life cycle, suggesting that they may be promising antimalarial drug targets. PDE inhibitors are used safely to treat a range of noninfectious human disorders. Here, we report three subseries fast-acting and potent Plasmodium falciparum PDEβ block asexual blood-stage development also active against clinical isolates. Two inhibitor have transmission-blocking activity by targeting PDEs...
Human adaptive natural killer (NK) cells have diminished reliance on accessory cytokines for their activation whilst being efficiently activated by infected host in conjunction with pathogen specific antibodies. Here, we show that potent antibody-dependent NK cell responses are induced Plasmodium falciparum erythrocytes (iRBC) peripheral blood mononuclear (PBMC) from malaria-exposed Gambian individuals the presence of autologous sera, which absent those malaria-naïve UK individuals. However,...
Summary The efficacy of current antimalarial drugs is threatened by reduced susceptibility Plasmodium falciparum to artemisinin. In the Mekong region this associated with mutations in kelch propeller-encoding domain pfkelch13 , but variants other parasite proteins are also thought modulate response drug. Evidence from human and rodent studies suggests that μ-subunit AP-2 adaptin trafficking complex one such protein interest. We generated transgenic parasites encoding I592T variant pfap2μ...
In vitro permeation studies using nail clippings or plates are commonly used in the development of transungual formulations. However, there ethical, safety and cost issues associated with sourcing such tissues. Herein, we describe a preliminary approach is described for design manufacture human model surrogate based on 3D printing. To evaluate these printed constructs, nails were mounted conventional glass Franz cells commercial antifungal lacquer formulation containing ciclopirox olamine...
Abstract Tackling relapsing Plasmodium vivax and zoonotic knowlesi infections is critical to reducing malaria incidence mortality worldwide. Understanding the biology of these important related parasites was previously constrained by lack robust molecular genetic approaches. Here, we establish CRISPR-Cas9 genome editing in a culture-adapted P. strain define parameters for optimal homology-driven repair. We scalable protocol production repair templates PCR demonstrate flexibility system...