Derrick K. Mathias, PhD, MPH
Why do some blood-feeding arthropods transmit pathogens while others do not? A large number of hematophagous arthropods, including mosquitoes, ticks, sand flies, fleas, black flies, kissing bugs, and tsetse, transmit a wide array of viruses, parasites, and bacteria that cause human disease. However, the degree of variation among arthropods in their ability to harbor and transmit pathogens (i.e., variation in vector competence) is tremendous. Understanding the molecular biology that underlies this variation may lead to novel interventions that not only save lives but improve the quality of life, particularly in developing countries where vector-borne diseases often have the greatest impact.
My research focuses on host-pathogen interactions in arthropod-borne disease systems that require propagation and/or development within the arthropod vector prior to human transmission. Such cyclopropagative and cyclodevelopmental transmission requires pathogens to negotiate multiple barriers to infection within the arthropod before transmission to a human host can occur. Currently, I’m investigating the molecular processes that take place when malaria parasites (Plasmodium falciparum) encounter the midgut of Anopheles mosquitoes following an infectious blood meal. For the parasite to successfully complete its life cycle, the Plasmodium ookinete must attach to and invade the midgut epithelium before forming an oocyst in the basal lamina of this tissue. This is an obligate step in the parasite’s life cycle and is one that underscores the importance of understanding the molecualr biology of mosquito-midgut epithelial cells, as they serve as a primary barrier to infection to not only malarial parasites, but to arboviruses as well.
My interest in vector-pathogen interactions and variation in vector competence among arthropods has steered my research towards understanding glycosylation, a common post-translational modification (PTM) involving the addition of saccharide molecules (glycans) to proteins. In actuality, a range of PTMs fall under the heading of glycosylation, including simple O-linked glycans, complex highly-branched N-linked glycans, and the long, sulfated chains of disaccharides characteristic of glycosaminoglycans. Numerous pathogens use glycans and glycoproteins as ligands for attachment and invasion of host tissues. Thus, understanding their role in the molecular biology of vector-pathogen interactions and investigating glycosylation in a comparative, evolutionary framework may shed light on variation in vector competence. Furthermore, glycans play prominent roles in fundamental biological processes, including protein folding, cell adhesion, and embryonic development, yet glycosylation is an understudied subject that has been largely ignored by evolutionary biologists. Thus, another goal of my postdoctoral fellowship is to develop a line of basic research into understanding how glycan structures evolve using dipterans as a model, focusing particularly on divergence within and between lineages of mosquitoes and fruit flies. Research in fruit flies has revealed important roles of O-linked glycans in embryonic development but functions of glycans in the physiology of adult mosquitoes and flies are woefully understudied.