Professor Inke Nathke
Life Sciences Office, School of Life Sciences
+44 (0)1382 385821
SLS Research Complex
Morphogenesis in development and tissue maintenance requires an intricate balance between cell-cell interactions, cell-proliferation, cell migration and differentiation. Loss of the co-ordination between these processes prohibits proper development and is also involved in tumour formation. The long-term goal of research in my laboratory is to understand how cellular adhesion, migration, and cell division are regulated in concert during development and differentiation and how changes in these processes contribute to tumour formation.
See Figure 1 below: This Figure shows a PTK cell in early mitosis stained for APC protein (red), the kinetochore marker Crest (green), DNA (blue), and tubulin (magenta). APC localises to the outside of the kinetochore where tubulin is attached
My particular focus is the adenomatous polyposis coli protein, a large cytoplasmic protein that has been implicated in a variety of basic cellular processes including cell migration, cell adhesion, and proliferation. APC binds to beta-catenin and regulates its intracellular concentration. Beta-catenin is an important mediator of cell adhesion and also plays a role in regulating the activity of specific transcription factors. APC also interacts directly and indirectly with cytoskeletal proteins and regulates their stability. Its multi-functional nature places APC at the interface between regulation of cellular architecture and differentiation programs and this may explain the high penetrance of APC mutations, particularly in the intestinal tract: APC mutations constitute an extremely early stage of inherited as well as sporadic colon cancer. In addition, patients with somatic deletions in one of the APC alleles, have an increased risk for developing brain tumours and other epithelial abnormalities.
See Figure 2 below: The image shows whole mount mouse intestinal tissue that was stained with phalloidin and DAPI to visualise F-actin and DNA. F-actin concentrates mostly in the brush border of the apical surface particularly in differentiated enterocytes in the upper part of villi that face the gut lumen and are seen here. This type of detailed image allows correlations between changes in the overall morphology of intestinal and colonic tissue with specific mutations.
The aim of work in my laboratory is to determine the molecular mechanisms that govern the role of the APC protein in cell migration, adhesion and division and includes investigating the relationship between different protein interactions of APC in vivo. The experimental approaches we use include whole tissue, cultured cells, in vitro assays combined with cellular and molecular biology techniques as well as high-resolution fluorescence microscopy.
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