Inflammation is generally a good process that helps us as individuals cope with infection and disease. However inflammatory responses can go wrong generating either too much or too little inflammation.
Many diseases are associated with mistakes in the inflammatory process such as chronic inflammatory conditions (e.g. inflammatory bowel disease, rheumatoid arthritis) or inadequate inflammatory responses (e.g. some cancers).
The Irving lab uses a combination of Biochemistry, Molecular and Cell Biology to investigate these diseases. We are interested in understanding the molecular interactions in signal transduction networks regulating inflammation.
Research areas
Modulating the innate immune system to control inflammation
Inflammatory responses form one of the first lines of defence to infections and other immune challenges. Inflammation is a key modulator of many chronic conditions where inflammatory response are not working properly. The innate immune system forms a key part of this process and our group is interested in how the innate immune responses can be regulated. Using systems biology approaches, we have identified cryptic enzymatic centres in proteins that modulate the innate immune response. Our goals are to identify how these less explored molecular mechanisms can be used to dampen or heighten the innate immune response. We are approaching this task in several ways incorporating modern molecular and cellular analytical and imaging techniques. Projects in this area explore the scaffold of the novel catalytic centres and how the molecules interact with other proteins in vitro and in vivo. A better understanding of the biological role and mechanism of these cryptic centres will potentially lead to enhanced rational drug design to therapeutically modulate the action of these immune proteins.
Visualizing molecules to develop precision medical tools
Molecular imaging is used to understand how proteins interact and relay information within cells. This approach has been most informative and lead to much greater understanding of the mobility and interactions of proteins. For instance, we are using fluorescently tagged subunits of an ion channel to monitor the distribution of the subunits and complete ion channel complex in the cell. Often the proteins are tagged with large fluorescent proteins that by their sheer size may interfere with natural processes and thereby bias our understanding. To counter this potential problem, we also are investigating how we can use smaller fluorescent molecules to monitor protein function. Projects in this area investigate different aspects of protein complex formation and protein function using modern molecular, cellular imaging and analytical techniques.
Haplotyping as a method to improve precision medicine
Haplotyping refers to the process of separating the genomic information into the specific information inherited from your mother and father. This process is sometimes called phasing and refers to the physical linkage of chromosomal polymorphisms. Phasing is important as genetic information present on one chromosome may modulate protein expression by overriding the information on the other parental chromosome and affect the patient’s response to drugs or influence how immune function is affected in bone-marrow transplantation. Projects in this area are focussed on how haplotypes affect immune responses and use modern tissue and molecular processing techniques combined with next generation sequencing and data analysis processes.
