Delineating immune circuits for innate and adaptive immune protection (2020–2022)
Abstract:
The immune system provides the essential framework to protect us against infection, disease and to heal tissues after trauma. This is achieved by
a complex but elegant network of different types of white blood cells including T cells, natural killer (NK) cells and innate lymphoid cells
(ILCs). These cells form the innate (first) and adaptive (specific) responders of the immune army that seek out and destroy disease-causing
organisms to ensure long-term immune protection. Transcription factors drive the regulatory circuits essential to control these cell types and their
diversity. This diversity is critical for the generation of the wide variety of regulatory and effector cell types required to safeguard the host
against both pathogens and cancers. A fundamental challenge in understanding the function of the immune system is to elucidate how complex
transcriptional circuits regulate specific developmental switches, cellular plasticity and heterogeneity to allow the emergence of multiple
different cell lineages with potent effector functions adapted to effectively control disease. The principal aim of this research is to understand the
cellular and molecular programs that control immune cell specification, diversity and function allowing the induction and maintenance of
protective immunity.
This proposal will investigate pivotal molecular aspects of immune cell differentiation and regulation by addressing the following major
scientific aims: 1. Transcriptional regulation of peripheral T cell differentiation; 2. Delineation of the transcriptional regulation of innate
lymphoid cells; and 3. Elucidation of the role, regulation and plasticity of these cells during infection. Understanding these features is critical for
the immune system to be capable of generating and maintaining all these lineages throughout the life of an individual and our ability to mimic
these properties in vaccination approaches or therapeutic intervention.
