Dr Dave Boucher

Research

Research

Proteolytic network in innate immunity 

Our lab study how the human body generate inflammation in response to various assaults. Current research focuses on understanding how the human innate immune system recognizes and responds to bacterial infection.  We are especially interested to understand how a protein signalling complex called the inflammasome is doing so in the human body.

During infection, bacteria activate the inflammasomes by direct recognition of cytoplasmic receptors. Those multiprotein complexes activate proteases called inflammatory caspases. Humans genome encode for three inflammatory caspases: caspase-1, -4, and -5. Once activated, those enzymes cleave specific proteins in the cells to coordinate an immune response.

How are inflammatory caspases activated?

In recent years, we studied how caspase-1 is activated during inflammation (Boucher et al., J. Exp. Med. 2018). We found an intrinsic mechanism that control the duration of caspase-1 activity and coordinate inflammation in healthy individuals.

However, our knowledge of the inflammasome that activates caspase-4 and -5 and the mechanisms that control their activity is much more limited. We are currently working to understand how those enzymes are activated in response to Gram-negative bacterium infection and how their activity is regulated.

What are the consequences of caspases activation?

The activation of inflammatory caspases enables the secretion of pro-inflammatory cytokines (IL-1ß and IL-18) and the execution of a programmed form of cell death called pyroptosis. Those responses are essential to restrict pathogen proliferation and to clear infections efficiently. However, when uncontrolled, inflammasome overactivation can have adverse consequences (e.g., sepsis, arthritis)

Recently our research highlighted novel functions of the inflammasomes in specific cell types (Chen*, Monteleone* and Boucher* et al., Sci. Immunol 2018). Building on this research, we aim to understand how specific tissue uses inflammasome to respond to bacterial infections.

We use a combination of biochemical and cell biology approaches to clarify the roles of inflammasomes and caspases in inflammatory diseases (e.g., autoimmune disease, sepsis, bacterial infection, parasites infection). Inflammasome recently emerged as a key player in various conditions with an inflammatory component like lifestyle diseases (diabetes, obesity), infectious diseases (Salmonella, E.coli), and genetic diseases. A better understanding of inflammasome and inflammatory caspases biology will support the development of novel therapeutics against those diseases.

Teaching and scholarship

Teaching

I am a cell biologist and biochemist who studies innate immunity. With my teaching, I aim to inspire and motivate the next generation of scientists. I believe that excellent lectures are accessible, engaging, interactive, and helps students to acquire key scientific concepts.

Tutorial

I run a stage 2 tutorial for students in biology, biochemistry, and biomedical science. During those tutorials, I discuss with students many aspects of the innate immune system with an emphasis on inflammasomes. We cover various aspects of inflammasome biology ranging from biochemistry to their involvement in diseases.

Project

Final year projects in my laboratory explore how different immune cell types activates the inflammasome and respond to infections. Various aspects of inflammasomes biology are touched, from biochemistry, microbiology to cell biology. Those projects align with the current interests in the lab and are designed to familiarise students with various techniques.