The researchers at CIMR provide a unique partnership between basic and clinical research, aimed at understanding the cellular basis of disease. A major thrust of our work is to use insights from genetic disease to reveal mechanisms that control cell biological processes, and conversely to use cell biology to understand mechanisms of disease. Crucial to this is the use of multiple approaches, including genetics, and cellular and structural biology.
Current strengths include both cell biological and physiological themes as well as particular groups of diseases. However, our research captures a broad range of diseases, and it is this breadth that will allow the work at CIMR to reveal fundamental principles of disease development.
Cell biological themes:
Protein homeostasis and folding. Protein homeostasis is essential for cell growth and damage control. We are interested in the mechanisms that determine protein turnover, and how specific proteins are tagged and targeted for proteasomal degradation. Proteins must be correctly folded for their normal function, and our researchers study how cells respond to excess unfolded proteins, and how misfolded proteins are selected for endoplasmic-reticulum-associated degradation.
Intracellular membrane traffic. Cell function requires constant communication between organelles, and protein delivery to the correct subcellular site. Our scientists work on the detailed mechanisms by which proteins traffic through the secretory and endocytic pathways, and the adaptations of this machinery in specific tissues such as neurons. A crucial aspect of membrane traffic is the homeostasis of lipids, the building blocks of membranes.
Cellular mechanisms of infection and immune cell function. We aim to understand how the immune system ensures that our body remains healthy despite continual invasion by bacteria and viruses, and conversely the mechanisms that pathogens use to subvert immune defence. Another goal is to understand the interplay between different immune cell types in ensuring normal adaptive immunity.
Stem cell biology. Haematopoietic stem cells (HSCs) give rise to all blood cell types. Several groups focus on complementary aspects of haematopoietic stem cell biology, including the transcriptional networks that control differentiation and renewal, and the role of specific signalling pathways. These groups are also members of the Cambridge Stem Cell Institute (SCI) and will move into the new SCI institute building in 2017/18.
Neurodegenerative disease. Protein misfolding and aggregration underlies all the major neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Huntington’s disease. Our research aims to identify which misfolded proteins and which mutations lead to disease, as well as ways to intercept this through protective processes such as autophagy.
Haematological disorders. Several of our groups study how HSC dysfunction can give rise to blood disorders. In addition, another focus is the control of blood clotting, which must be tightly regulated to avoid thrombosis or conversely excessive bleeding.
Immunological and infectious disease. We study the mechanisms of pathogenesis by several bacteria and viruses, including Shigella, Herpesvirus and Mycobacteria. Our researchers also analyse genetic diseases of the immune system to understand the cell biology of immune cells, as well as autoimmune diseases, which arise when immune cells start to recognize and destroy normal healthy tissue. This includes both inflammatory diseases and type I diabetes.
Inherited neurological disorders. Insights from the clinic are essential for our investigation into the causative genes for inherited disorders. Our researchers aim to characterize the pathogenic mechanisms by which a mutation leads to the disease phenotype and current areas of focus include intellectual disability and Mendelian disorders of painlessness and excess pain.