Bio-Metrology and Modelling of a Complex System: The Malaria Parasite

Disruption of Plasmodium falciparum kinetochore proteins destabilises the nexus between the centrosome equivalent and the mitotic apparatus

J Li, GJ Shami, B Liffner, E Cho, F Braet, MT Duraisingh, S Absalon, MWA Dixon, L Tilley

2024-12-01

Plasmodium falciparum is the causative agent of malaria and remains a pathogen of global importance. Asexual blood stage replicati..

Plasmodium falciparum formins are essential for invasion and sexual stage development

S Collier, E Pietsch, M Dans, D Ling, TA Tavella, S Lopaticki, DS Marapana, MA Shibu, D Andrew, S Tiash, PJ McMillan, P Gilson, L Tilley, MWA Dixon

2023-12-01

The malaria parasite uses actin-based mechanisms throughout its lifecycle to control a range of biological processes including int..

Repurposing the mitotic machinery to drive cellular elongation and chromatin reorganisation in Plasmodium falciparum gametocytes

J Li, GJ Shami, E Cho, B Liu, E Hanssen, MWA Dixon, L Tilley

2022-12-01

The sexual stage gametocytes of the malaria parasite, Plasmodium falciparum, adopt a falciform (crescent) shape driven by the asse..

Deletion of the Plasmodium falciparum exported protein PTP7 leads to Maurer’s clefts vesiculation, host cell remodeling defects, and loss of surface presentation of EMP1

OMS Carmo, GJ Shami, D Cox, B Liu, AJ Blanch, S Tiash, L Tilley, MWA Dixon

2022-08-01

Presentation of the variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (EMP1), at knob-like protrusions on the ..

Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy

SC Xie, RD Metcalfe, E Dunn, CJ Morton, SC Huang, T Puhalovich, Y Du, S Wittlin, S Nie, MR Luth, L Ma, MS Kim, CFA Pasaje, K Kumpornsin, C Giannangelo, FJ Houghton, A Churchyard, MT Famodimu, DC Barry, DL Gillett

2022-06-03

Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously u..

Dimeric Artesunate Glycerophosphocholine Conjugate Nano- Assemblies as Slow-Release Antimalarials to Overcome Kelch 13 Mutant Artemisinin Resistance

Y Du, C Giannangelo, W He, GJ Shami, W Zhou, T Yang, DJ Creek, C Dogovski, X Li, L Tilley

2022-05-01

Current best practice for the treatment of malaria relies on short halflife artemisinins that are failing against emerging Kelch 1..

Multimodal imaging reveals membrane skeleton reorganisation during reticulocyte maturation and differences in dimple and rim regions of mature erythrocytes

AJ Blanch, J Nunez-Iglesias, A Namvar, S Menant, O Looker, V Rajagopal, WH Tham, L Tilley, MWA Dixon

2022-01-01

The red blood cell (RBC) is remarkable in its ability to deform as it passages through the vasculature. Its deformability derives ..

Safety, infectivity and immunogenicity of a genetically attenuated blood-stage malaria vaccine

R Webster, S Sekuloski, A Odedra, S Woolley, H Jennings, F Amante, KR Trenholme, J Healer, AF Cowman, EM Eriksson, P Sathe, J Penington, AJ Blanch, MWA Dixon, L Tilley, MF Duffy, A Craig, J Storm, JA Chan, K Evans

2021-12-01

Background: There is a clear need for novel approaches to malaria vaccine development. We aimed to develop a genetically attenuate..

Design of proteasome inhibitors with oral efficacy in vivo against Plasmodium falciparum and selectivity over the human proteasome

SC Xie, RD Metcalfe, H Mizutani, T Puhalovich, E Hanssen, CJ Morton, Y Du, C Dogovski, SC Huang, J Ciavarri, P Hales, RJ Griffin, LH Cohen, BC Chuang, S Wittlin, I Deni, T Yeo, KE Ward, DC Barry, B Liu

2021-09-28

The Plasmodium falciparum proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates..

Surface area-to-volume ratio, not cellular viscoelasticity, is the major determinant of red blood cell traversal through small channels

A Namvar, AJ Blanch, MW Dixon, OMS Carmo, B Liu, S Tiash, O Looker, D Andrew, LJ Chan, WH Tham, PVS Lee, V Rajagopal, L Tilley

2021-01-01

The remarkable deformability of red blood cells (RBCs) depends on the viscoelasticity of the plasma membrane and cell contents and..

Multimodal analysis of Plasmodium knowlesi-infected erythrocytes reveals large invaginations, swelling of the host cell, and rheological defects

B Liu, AJ Blanch, A Namvar, O Carmo, S Tiash, D Andrew, E Hanssen, V Rajagopal, MWA Dixon, L Tilley

2019-05-01

The simian parasite Plasmodium knowlesi causes severe and fatal malaria infections in humans, but the process of host cell remodel..

A new Python library to analyse skeleton images confirms malaria parasite remodelling of the red blood cell membrane skeleton

J Nunez-Iglesias, AJ Blanch, O Looker, MW Dixon, L Tilley

2018-01-01

We present Skan (Skeleton analysis), a Python library for the analysis of the skeleton structures of objects. It was inspired by t..

Erythrocyte β spectrin can be genetically targeted to protect mice from malaria

PM Lelliott, HM Huang, MW Dixon, A Namvar, AJ Blanch, V Rajagopal, L Tilley, C Coban, BJ McMorran, SJ Foote, G Burgio

2017-12-12

The malaria parasite hijacks host erythrocytes to shield itself from the immune system and proliferate. Red blood cell abnormaliti..

A dynamic stress model explains the delayed drug effect in artemisinin treatment of Plasmodium falciparum

P Cao, N Klonis, S Zaloumis, C Dogovski, SC Xie, S Saralamba, LJ White, FJI Fowkes, L Tilley, JA Simpson, JM McCaw

2017-12-01

Artemisinin resistance constitutes a major threat to the continued success of control programs for malaria, particularly in light ..

A mechanistic model quantifies artemisinin-induced parasite growth retardation in blood-stage Plasmodium falciparum infection

P Cao, N Klonis, S Zaloumis, DS Khoury, D Cromer, MP Davenport, L Tilley, JA Simpson, JM McCaw

2017-10-07

Falciparum malaria is a major parasitic disease causing widespread morbidity and mortality globally. Artemisinin derivatives—the m..

Initiation of gametocytogenesis at very low parasite density in Plasmodium falciparum infection

R Farid, MW Dixon, L Tilley, JS McCarthy

2017-04-01

The recent focus on the elimination of malaria has led to an increased interest in the role of sexual stages in its transmission. ..