Prof. Yvette van Kooyk, Spinoza laureate and world expert in glyco-immunology, has unraveled how altered glycan structures dysregulate the immune system during the development of cancer, autoimmune disease and infectious diseases such as HIV/AIDS. She discovered that certain sugar molecules can stimulate – or, indeed, inhibit – communication between immune cells. Van Kooyk uses her knowledge to develop nano-medicines that support the immune system in its fight against cancer and dampen immunity in allergy.
Research Focus of Prof. Ian Wilson: Structural Studies of the Immune System, Viral Pathogens, and Vaccine Design
Much of his recent work is focused on HIV-1 and influenza viruses. The 1918 flu, which killed 20-40 million people worldwide, is being investigated through structural and binding studies of the 1918 viral proteins, such as the hemagglutinin (HA) and neuraminidase, as well as other the viral proteins. The avian H5N1 and swine H1N1 influenza virus HA structures have been determined as well as mutations that enhance binding to human receptors that may allow the virus to cross the species barrier into humans and be transmissible. His research team has also determined structures of almost all of the rare, broadly neutralizing antibodies against the HIV-1 envelope proteins, gp120 and gp41, in order to elucidate the sites of vulnerability that can be used for HIV-1 vaccine design. A very exciting project on broadly neutralizing antibodies with influenza virus has revealed novel epitopes that are of great value for structure-assisted vaccine development. They have defined a broadly neutralizing epitope in all group 1 influenza subtypes and are working on other antibodies that recognize group 2 as well as those that cross all subtypes. Other flu projects are associated with the nucleoproteins, polymerases and neuraminidases in order to understand how influenza replicates.
The research developed by the laboratory led by Miguel Soares at the Instituto Gulbenkian de Ciência revolves around understanding the cellular and molecular mechanisms regulating inflammation, immunity and disease tolerance.
Immunity evolved in multicellular organisms to limit the potential negative impact resulting from continuous exposure to microbes. Innate and adaptive components of the immune system are endowed with the capacity to sense and target pathogenic microorganisms for containment, destruction or expulsion as the means to preserve organismal homeostasis and fitness. Resistance to infection refers to the output of these immune functions. Multicellular organisms also evolved another defense strategy that preserves organismal homeostasis and fitness without exerting a direct negative impact on microorganisms. This defense strategy, referred to as disease tolerance, relies on evolutionarily conserved stress and damage responses that limit the extent of metabolic dysfunction and damage imposed on parenchyma tissues, either directly by pathogenic microorganisms or indirectly by immune-driven resistance mechanisms.
The overall aim of the Soares Laboratory is to identify and characterize these stress and damage responses which confer tissue damage control and establish disease tolerance to infection. The central hypothesis tested is that a functional interplay between immune-driven resistance mechanisms, and stress and damage responses acting in parenchyma tissues, exists to limit, counter and repair the pathogenic effects of infection.
Understanding the cellular and molecular mechanisms governing this network of interactions and responses should be transformative in our understanding of host-microbe interactions, with direct impact on the treatment of infectious diseases.