Problem Statement
My project is trying to tackle the problem of emerging drug resistance in the malaria parasite by developing therapeutics targeting protein-lipid interfaces, which could serve as an invaluable tool for achieving high selectivity efficacy in abolishing lipid-dependent activation of drug targets during malaria infection.
Progress Highlights
I have established a recombinant protein expression platform at ACENTDFB, Abu Zaria, where we have produced the recombinant PfLBPs on a large scale and commenced biophysical characterization of the PfLBPs for precise drug targeting. Community engagement, human blood sample collection, capacity building, and training of field mentees in ex vivo parasite culture are all directed at testing the efficacy of drug targets against clinical parasite isolates.
Key Findings
Identification of novel Plasmodium falciparum lipid-binding proteins and a high affinity binder which is currently under further evaluation.
Potential Impact
Targeting the malaria parasites' lipid-binding proteins have promising potentials for the development of new antimalarial intervention.
Summary
Current estimates indicates that at least one to three million children die from malaria infection yearly in Africa alone. The emergence of drug-resistant parasite strains poses a major threat to global health and economy with devastating impact on sub-Saharan Africa. This project hopes to design drug-like molecules that could precisely target specific proteins with lipid-binding modules associated with the drivers of antimalarial drug resistance. This long-awaited intervention strategy for controlling the risk of anti-malarial drug resistance in the African continent and other endemic parts of the world would be of immense importance. Also, the project will engage community members with the aim of bridging the gap between researchers and the communities while emphasizing their participations during field sampling in the current drive-out malaria efforts.
Grantee Description
Dr. Emmanuel Amlabu is a Senior academic staff and the malaria research group leader at the Genomics and Molecular Biotechnology Research and Training Laboratory (GMBRTL) in Prince Abubakar Audu University, Anyigba, Nigeria. He obtained his PhD in Life Sciences from the Jawaharlal Nehru University, New Delhi and his doctoral work focused on the molecular biology of Plasmodium falciparum erythrocyte invasion. During his postdoctoral research at the West African Centre for Cell Biology and Infectious Pathogens (WACCBIP), University of Ghana, and the Francis Crick Institute, UK, he profiled a pipeline of merozoite proteins for vaccine development and precise drug targeting.
Dr. Amlabu now works on the development of novel antimalarial therapeutics targeting Plasmodium falciparum lipid-binding proteins. He is passionate about creating opportunities for next generation scientists that will pilot the most vibrant research platforms in Africa, and provide an excellent environment for the development of future science research leaders.
Project: Development of novel antimalarial therapeutics targeting Plasmodium falciparum lipid-binding proteins (ARISE-PP).
In the ARISE-PP project, we are working towards biophysical characterisation of the individual protein-binding events to illuminate their avidity or selectivity toward lipids and define the essentiality of genes encoding Plasmodium falciparum lipid-binding proteins (PfLBPs) in phosphoinositide signalling pathway. We plan to obtain deeper mechanistic insights on how protein-lipid interactions mediate a plethora of cellular effects by solving the crystal structure of the recombinant PfLBPs. Also, we will characterise the structural determinants involved in the interaction between the PfLBPs and PIPs which should inform downstream drug design approaches. We will build on these strategic approaches by testing newly synthesised drug-like molecules in parasite growth inhibitory assays and establish their potency against drug-resistant parasites, with the sole aim of providing baseline data for hit-to-lead development of PfLBP-based inhibitors.
