Research
Researchers in the Department of Microbiology and Immunology are at the forefront of groundbreaking discoveries in the following areas:
Antimicrobial Discovery and Resistance
Antimicrobial-resistant infections represent a top threat to public health worldwide. We are investigating how microbes develop resistance to frontline antibiotic and antifungal drugs and devising novel strategies to circumvent these mechanisms. Using high-throughput approaches to screen natural products and small molecule libraries, our researchers are uncovering new chemical scaffolds with potent antimicrobial activity. Looking beyond drugs that directly target microbes, we are also exploring new frontiers in host-directed therapeutics, anti-biofilm agents, and modulators of the immune response to infection. By illuminating new ways to combat microbes from multiple angles, we hope to help develop effective antimicrobials for Mycobacterium tuberculosis, cystic fibrosis bacteria such as Pseudomonas aeruginosa, and other drug-resistant pathogens.
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Antivirals and Vaccines
The COVID-19 pandemic highlighted the devastation that viruses can cause and the need for both protective and therapeutic measures to combat them. Our researchers are characterizing genes and proteins involved in the viral lifecycle to understand how viruses such as influenza A, hepatitis C, and Zika hijack the host cell, paving the way for novel avenues for intervention. We are mining both natural and synthetic sources for host-directed antiviral compounds, which display broad-spectrum activity toward a wide range of current and emerging viruses. Using a suite of multi-omics approaches, our researchers are working to identify molecular pathways in immune cells and structures that can be leveraged to enhance the potency of vaccines. We are also investigating strategies to amplify the immune response to viral pathogens to boost the body’s natural defense mechanisms against infection.
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Autoimmunity and Inflammatory Disease
Uncontrolled immune responses can damage healthy cells and tissues, leading to autoimmune and inflammatory diseases. Using in vitro, in vivo, and computational approaches, our researchers are mapping the complex signaling pathways between various types of immune cells and investigating how these dynamics drive immune dysregulation. We are working to understand how acute viral infection and other environmental factors influence the development of autoimmune diseases including multiple sclerosis, type 1 diabetes, and arthritis, how abnormal activation of phagocytes triggers inflammation in diseases such as asthma, sepsis, and inflammatory bowel disease, and how interactions between the resident virome and the immune system contribute to autoimmunity in lupus. These and other projects will reveal new therapeutic strategies to reign in harmful immune attacks while maintaining beneficial immune activity.
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Cancer Immunity and Immunotherapy
Novel approaches to treating cancer rely on an understanding of how we can recruit and activate the immune system to target cancer cells. Our researchers are investigating the fundamental immunological processes involved in cancer cell detection and clearance and exploring how immunodeficiency contributes to cancer progression. We are studying the complex tug-of-war between cancer cells and the immune system, including how cancer cells can release chemical signals that create an immunosuppressive tumor microenvironment, downregulate antigen presentation to evade immune surveillance, and undergo changes in gene expression to support unchecked growth and proliferation. We hope to lay the groundwork for new cell therapies, antibodies, vaccines, and other immunotherapies that can restore, enhance, and direct the immune response to treat a range of intractable cancers.
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Host-Pathogen Ecology and Evolution
Today’s rapidly changing world is bringing about new sources of infectious disease and new opportunities for contact between hosts and pathogens. Using a combination of mathematical modelling, experimentation, and field work, our researchers are working to uncover the principles guiding the evolution, transmission, and virulence of key pathogens of global health priority. We are exploring the effects of climate change on host-pathogen distribution and interaction, the relationship between biodiversity loss and resistance to infection in host populations, and the influence of a host’s microbiome on its susceptibility to disease. This work will help to shape infectious disease mitigation strategies, inform the development of therapeutics with long-term efficacy, and bolster pandemic preparedness.
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Microbial Communities
Communities of microorganisms are found everywhere from the Earth’s oceans and soil to the human gastrointestinal tract and skin. Our researchers are characterizing how environmental disturbances such as forest fires and ocean warming and acidification impact the makeup of natural microbial communities and investigating the ripple effects on larger ecosystems. We are also working to understand how communities of microbes that reside within the body communicate with distant organs to influence human health. By studying both animal models and clinical samples, we are learning how dysbiosis in the microbiome contributes to a range of neurodegenerative, endocrine, and immunological diseases. We hope that this work informs new therapeutic strategies to use specific microbe species or the signaling metabolites they produce to restore homeostasis.
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Microbial Factories
Microorganisms are the factories that drive critical biogeochemical processes, from nutrient cycling to energy conversion. By analyzing these microbe-powered reactions, our researchers are uncovering detailed mechanistic insight into Earth’s natural systems and unlocking new innovations in biotechnology. We are studying how microbes use carbon under various environmental conditions, providing data to feed into computational models of the global carbon cycle. Furthermore, we are exploring how we can leverage catalytic and catabolic processes in microbes for a range of industrial applications, including developing new sources of renewable energy, efficiently synthesizing valuable materials, and breaking down waste.
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Microbial Physiology and Pathogenesis
Fundamental understanding of microbial physiology and function can unlock valuable insights into how microorganisms drive disease and illuminate new therapeutic targets. Our researchers are using high-resolution microscopy techniques to characterize bacterial secretion systems, sporulation, and other dynamic processes at the macromolecular level. We are employing cellular and biochemical assays to study novel mechanisms of intracellular invasion, replication, and survival. We are further analyzing protein structure, activity, and expression to investigate how key proteins contribute to microbial pathogenesis, particularly in the context of nutrient limitation, oxidation, and other forms of stress.