The Department of Bioengineering is honoured to welcome Dr Calvin Tiengwe, Assistant Professor in ³Ô¹ÏºÚÁÏ’s Department of Life Sciences, for our first Black History Month Department Seminar.
This is a special addition to our Department Seminar series and an opportunity to hear from an exceptional ³Ô¹ÏºÚÁÏ researcher working at the intersection of molecular parasitology, host–pathogen biology and global health.
Refreshments and networking will take place after this seminar in RSM 3.24
How does a cell count to one? Mechanisms of immune evasion in African trypanosomes
A fundamental problem in infection biology is how a parasite selects one member of a gene family from thousands of possibilities. Another is how changes to the expressed surface protein enable the parasite to alter its recognition by host antibodies. We seek to understand how trypanosome parasites orchestrate these two processes to evade host immunity. Each parasite must express one variant surface glycoprotein (VSG) at a time from a repertoire of over 2,500 genes to form a dense protective surface coat. Switching the VSG coat allows trypanosomes to sustain chronic infections. However, the molecular basis for enforcing the singular VSG choice is not completely understood.
I will describe two recent discoveries in this area. First, I will discuss the identification of ESBX, a key molecule required for full activation of the active VSG expression site and repression of silent sites, providing insight into how this singular gene choice is enforced. Next, I will describe a second source of variation at the trypanosome surface: the modification of VSGs with a simple set of sugar molecules that generate diversity in antibody epitopes. We identified ESAG3, the long-sought enzyme responsible for adding these sugars, and determined its cryo-electron microscopy structure, revealing an unusual 18-subunit molecular machine. I will also show how the sugars it adds influence antibody recognition. Together, these mechanisms allow trypanosomes to persist in their hosts and cause devastating disease in humans and animals in some of the world’s poorest populations. Our long-term goal is to engineer these epitopes to design vaccines that target these parasites.
Biography:
Dr Calvin Tiengwe is an Assistant Professor in the Department of Life Sciences, ³Ô¹ÏºÚÁÏ.
His research focuses on the molecular and cell biology of African trypanosomes, protozoan parasites that cause sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. His laboratory uses biochemistry, cell biology and structural biology approaches to understand how trypanosomes establish and maintain infection in the mammalian host, with a particular interest in surface antigen biology, immune evasion and parasite adaptation across diverse host microenvironments. Insights into their basic biology should expose vulnerabilities in these and related kinetoplastid parasites, which can be exploited to design better therapies and vaccines.
His long-term ambition is to connect mechanistic understanding with disease control efforts in communities where these infections persist.
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