Malaria is a mosquito-borne infectious disease, with its most severe form caused by the protozoan parasite Plasmodium falciparum. The rapid emergence and spread of drug‑resistant parasites demand new therapeutic strategies.

My PhD work defines the sources and mechanisms of cholesterol uptake in P. falciparum-infected RBCs and demonstrates how this pathway can be exploited to improve antimalarial drug delivery and therapeutic index.

In this talk, I will show how combining phylogenetic inference, protein structure prediction, and ancestral sequence reconstruction opens new ways to investigate how protein functions originate and diversify across the tree of life.

Just as the development of the first light microscopes uncovered a new microbial frontier, the use of high-throughput sequencing and metagenomics has uncovered a new frontier of unculturable microorganisms, often referred to as “microbial dark matter”.

Matthew's laboratory focuses on the incredibly multifunctional Omp85 protein superfamily which conduct essential processes in the outer membranes of all Gram-negative bacteria such as protein folding, insertion, and translocation reactions, as well as lipid transport reactions.

Throughout my PhD, I determined the transport mechanisms of two proteins that we show break the standard channel / transporter definitions and instead function as anion “chansporters” - proteins that exist somewhere on the spectrum between transporters and channels.

Heteromeric amino acid transporters (HATs) play essential roles in the transport of amino acids, thyroid hormones, and various amino acid–like drugs. Mutations in HATs are associated with several inherited disorders, including cystinuria, lysinuric protein intolerance, and autism spectrum disorders.

Autotransporters (ATs) are virulence factors found in Gram-negative bacteria that consist of three domains: an N-terminal signal peptide, a central passenger domain, and a C-terminal β-barrel domain. Here, we used RpeA from rabbit enteropathogenic Escherichia coli as a model AT.

The ability of Plasmodium falciparum to access and utilise vital nutrients, including riboflavin (vitamin B2), is essential for its growth and proliferation, positioning riboflavin metabolism as a promising target for antimalarial intervention.

My work studies how platelets control malarial infection, and through this has revealed the specific anti-plasmodial actions of platelets and molecules with novel mechanisms of parasite killing.

Leveraging artificial intelligence and deep learning to generate proteins de novo has unlocked new frontiers of protein design. This approach can be used to design bespoke binders that target specific proteins and domains.

Pantothenate, a precursor of the fundamental enzyme cofactor coenzyme A (CoA), is an essential nutrient for the intraerythrocytic stage of the human malaria parasite Plasmodium falciparum.