The cell is the basic unit of all life forms. to understand the cell, we must know all of its component parts & have a detailed mechanistic Understanding of how these function.
Our research interests in the area of Cellular and Molecular Structure and Function range from computational protein folding to stem cell biology. Despite the breadth, there are a number of themes that can be identified, all of which are centred on understanding fundamental mechanisms. Several labs are focussed on neuronal development and neuronal tissue function, for example, work that includes the study of neuronal stem cell generation, axon guidance mechanisms and the molecular basis for neural network formation. Central to these efforts is the study of stem cells and the use of a number of different animal models. Cutting-edge techniques involving laser optics and optogenetics are leveraged to study higher-order functions such as learning, memory and locomotion. Stem cells and animal models, including the zebra fish, are also being used to study development and disease in other systems and tissues including the heart and kidney. Collectively, the advances emerging from these efforts are expected to contribute to novel approaches to treating neural and heart tissue damage, brain cancers in children and Alzheimer's disease in the elderly to name just a few.
Genome stability through successive cell divisions is central to the maintenance of normal cellular function. Not surprisingly, DNA damage and the gain or loss of chromosomes or portions of them are hallmarks of cancer. Several MoGen labs are working to understand DNA repair mechanisms and the processes that ensure proper chromosome replication and segregation. In one collaborative effort, functional genomics, microscopy and mass-spectrometry are being used to study centrosome biogenesis, an important component in the regulation of cell division. In another collaboration, cell-based approaches and x-ray crystallography are utilized to determine how DNA repair enzymes are recruited to double-strand breaks.
Regulation of gene expression is critical at all stages in the life-cycle of a living organism, and control at both transcriptional and translational levels is the focus of many members of our Department. Core to the effort is the identification and characterization of the DNA- and RNA-binding proteins involved in controlling these processes. Over the past few decades, we have begun to appreciate the important roles played by small RNAs in gene regulation, and a new paradigm for small RNA-mediated gene regulation is beginning to emerge from recent work by MoGen labs. Splicing of pre-mRNA enables both gene regulation and the generation of varied protein isoforms, with exciting new work in this area from MoGen members shedding light on how microexon splicing is controlled in neural development and how the process is misregulated in autism.
The study of protein structure and protein interactions represents another theme among members of the group. Collectively, a wide range of biophysical techniques including NMR and x-ray crystallography, as well as computational approaches, are being used in this research. We study protein folding and quality control, protein-protein interactions, macromolecular assemblies, G protein-coupled receptors, ion transporters, virus-receptor interactions and protein kinases among others. Intrinsically disordered proteins are now known to mediate cross-talk between signalling pathways, and structural insights into how they perform this role represent one example of cutting-edge research that has recently emerged from our group. MoGen labs are also focussed on the development of novel protein and small-molecule human therapeutics, and notable among these efforts are the use of protein engineering to develop novel antibody therapeutics, the use of bacteriophage as antibiotics and the identification of new drug targets using the membrane yeast two-hybrid assay. Novel functional proteomic approaches are also being used to discover and characterize protein-drug and protein-ligand interactions, which promises to uncover new uses for already approved small-molecule therapeutics.
For a more detailed look at the work ongoing in the Cellular and Molecular Structure and Function research field please read the full Field Spotlight. Many members of the group are also associated with other research fields, and we invite you to explore them all.