Dr. Sonja Frölich caught our attention with her tweet demonstrating her use of ZEISS Airyscan super-resolution technology to study an organelle which the malaria parasite uses to invade red blood cells by analyzing thousands of samples in a non-biased, semi-automated fashion.
Dr. Sonja Frölich is a postdoctoral researcher at the Malaria Biology (Wilson) Laboratory located in the Research Centre of Infectious Diseases, the University of Adelaide, Australia. The focus of her work is in understanding the biophysical interactions between the malaria parasite and the human red blood cell (RBC).
Dr. Frölich is developing new approaches that dramatically improve visibility into the parasite proteins and underlying forces that control an essential organelle needed for RBC-entry, called the rhoptry, and thus replication of disease causing blood stage parasites.
Dr. Frölich, along with former postgraduate student, Benjamin Liffner, recently published a paper which describes how functional knock-down of a newly identified rhoptry-associated protein termed PfCERLI1 results in failure of the parasite to infect a red blood cell. This loss of infectivity could be targeted for the development of antimalarial compounds that reduce disease pathology in patients infected with malaria. We asked her to tell us more about her research.
Tell us about the Malaria Biology Laboratory.
The Wilson Lab applies multi-disciplinary approaches to understand the unique biology that allows malaria parasites to infect human red blood cells and cause disease.
By identifying and characterizing the key proteins that enable malaria parasites to infect red blood cells, we hope to identify new drug targets that can be developed to reduce the debilitating and costly burden of malaria.
In our recent publication, our approach was to develop a robust and quantitative super-resolution microscopy-based image analysis pipeline to characterize what happens when we removed PfCERLI1s function through gene-editing.
What findings did you recently publish?
Rhoptries, an essential organelle needed for RBC-entry, are ubiquitous throughout the phylum Apicomplexa, which includes some of the most important single-celled parasites of humans and animals. This specialized secretory organelle is located at the anterior pole of the parasite where it appears as a set of large club-shaped organelles. Upon contact with the host cell, the rhoptry organelles secrete proteins involved in early parasite attachment to the RBCs, mechanical entry and formation of a vacuole within which the parasite grows and replicates.
In the present study, we used electron microscopy, super-resolution (Airyscan) microscopy and computational image analysis to determine the subcellular localization of PfCERLI1 and the effect on rhoptry structure with PfCERLI1 depletion. Furthermore, RBC-entry and secretion assays in PfCERLI1 depleted parasites showed aberrations in proteolytic processing and blocked secretion of key rhoptry antigens which prevented the parasite from infecting red blood cells.