Special seminar Prof Hidde Ploegh

Virtual link https://uqz.zoom.us/j/88324477941

Abstract

Nanobodies are the recombinantly expressed variable domains of camelid ‘heavy chain only’ immunoglobulins. Their small size endows them with properties that make them ideal building blocks for a wide array of immunological applications. The use of short sequence motifs recognized by transpeptidases such as sortases (SrtA), or asparagine endoproteases (AEP) provides a labeling strategy that does not compromise their antigen binding properties. The ability to site-specifically modify nanobodies using such chemo-enzymatic transformations has enabled their use as imaging agents using positron emission tomography (PET). This
non-invasive imaging modality makes it possible to track immune responses in vivo, both anti-viral and anti-tumor responses. By equipping nanobodies with diverse payloads it is also possible to evoke a desirable immune response, or suppress autoimmunity. Several examples of these applications will be discussed,
including the development of potent anti-virals that afford prolonged protection against infection with influenza A and B viruses.

Biosketch

Hidde Ploegh is a biochemist whose area of interest is the immune system. He is known for his analysis of the pathways involved in antigen presentation by products of the Major histocompatibility Complex (MHC). Ploegh was born in 1953 in the Netherlands, where he attended Groningen University. He performed the work for his PhD at Harvard University and obtained his degree from Leiden University in 1981. He took a position as a junior group leader in the Institute for Genetics at the University of Cologne, Germany and in 1984 moved back to the Netherlands where he worked at the Netherlands Cancer Institute to head the Division of Cellular Biochemistry. In 1992 he was recruited to the Center for Cancer Research as a professor of biology at the Massachusetts Institute of Technology. In 1997 he joined the faculty of Harvard Medical School as the director of its graduate program in immunology. In 2005 he joined the Whitehead
Institute for Biomedical Research at the Massachusetts Institute of Technology. In 2016 Ploegh joined Boston Children’s Hospital. Ploegh is a member of EMBO, the American Academy of Arts and Sciences, the National Academy of Sciences and a correspondent of the Royal Dutch Academy of Sciences.

Research Interests

Ploegh’s laboratory studies the biochemistry of immune recognition. Earlier work centered on the analysis of the biochemical pathways involved in antigen processing and presentation by the products of the Major Histocompatibility Complex (MHC), which led to studies into glycoprotein biosynthesis and
glycoprotein trafficking more generally. The discovery that human cytomegalovirus exploits an unusual mechanism to dispose of Class I MHC products, critical for recognition of virus-infected cells by cytotoxic T cells, uncovered new aspects of glycoprotein quality control. Ploegh developed activity-based probes to study proteasomal proteolysis and more specifically the role of ubiquitin-specific proteases, also in the context of herpesvirus infections. More recently Ploegh has combined the generation of camelid-derived antibody fragments (‘nanobodies’) with a protein engineering approach, based on the use of bacterial sortases in conjunction with peptide chemistry. This combination not only enables the visualization, by non-invasive means, of anti-tumor and anti-virus immune responses using positron emission tomography, but can also be deployed to manipulate immune responses.

Hosted By
Professor David Craik
d.craik@imb.uq.edu.au