Atomic Force Microscopy and Structure of Plasmodium falciparum Circumsporozoite Protein and Lipid Rafts

This project can also be virtual.

A malaria vaccine that targets both human and mosquito infections, also known as a vaccine that interrupts malaria transmission, has the potential to benefit malaria elimination and eradication. The importance of developing such a vaccine is underscored by the lack of significant progress in reducing global malaria cases since 2015 (1, 2). The mission of LMIV is to develop malaria vaccines for pre-clinical and clinical testing including phase 1 and 2 human trials. Over the past two decades, LMIV has performed numerous clinical trials and currently has the leading transmission blocking vaccine, Pfs230D1-EPA, in a phase 2 trial in Mali (ClinicalTrials.gov Identifier: NCT03917654).
 
The scope of work for the BESIP intern is part of an ongoing collaboration among Dr. David Narum (Bldg. 29) in LMIV,/NIAID, Dr. Albert Jin (Bldg. 13) in LCIMB/NIBIB, and coworkers in the area of malaria vaccine development. The vaccine candidates and nano-carriers are produced using commercial platforms for recombinant protein expression, purification, and full biochemical and biophysical characterization in a manner suitable for scaled production and product development for early human trials. The BESIP intern shall join the ongoing investigation of the macromolecular structure and nanomechanical properties of a protein-protein conjugated malaria vaccine. More specifically, the summer project involves resolving the nanoparticle nature of a Plasmodium vivax Pvs230D1-EPA conjugated vaccine, an orthologous conjugated vaccine to Pfs230D1-EPA, using biological atomic force microscopy (Bio-AFM) and related analyses. We focus on using Bio-AFM to understand the structural properties of the biologic and aim to extend the AFM methodology for imaging and force spectroscopy of all macromolecules and nanostructures.

The BESIP intern may also engage in an ongoing investigation of the structure of the circumsporozoite protein (3) which is the active vaccine component in the GSK malaria vaccine RTS,S or MosquirixTM.  Specific details of the intern's work will be determined through discussions with the mentors.

1. WHO (2017) World Malaria Report 2017.
2. WHO (2018) World malaria report 2018. 210.
3. Herrera, R., Anderson, C., Kumar, K., Molina-Cruz, A., Nguyen, V., Burkhardt, M., Reiter, K., Shimp, R., Howard, R., Srinivasan, P., Nold, M., Ragheb, D., Shi, L., DeCotiis, M., Aebig, J., Lambert, L., Rausch, K., Murotava, O., Jin, A., Reed, S., Sinnis, P., Barillas-Mury, C., Duffy, P., MacDonald, N., Narum, D.L., (2015) Reversible conformation change in the Plasmodium falciparum circumsporozoite protein masks its adhesion domains.  Inf. Imm. 83:3771-3780