Dr. Kate Treharne

Research profile

My post-doctoral career has focused on the biochemical defects associated with the hereditary disease cystic fibrosis (CF). A single amino-acid deletion ( F508) is responsible for 80% of CF cases. CF results in a plethora of unexplained symptoms, such as cancer, osteoporosis, diabetes, which are manifesting themselves more as the CF population ages due to improved treatment. The defective gene was cloned in 1989 and its protein product (the cystic fibrosis transmembrane conductance regulator or CFTR) determined to be a chloride channel. This focused research almost exclusively on this aspect of the protein's function; however, work on this aspect of CFTR has not established a molecular function for F508. Thus, CF is an intensively-researched disease without a direct link between F508 and disease pathogenesis.

I have discovered a molecular interaction of the F508 CFTR region with the protein kinase CK2 and that CK2 binding is abolished by deletion of F508. This approach has led to a paradigm shift by establishing F508 in the normal CFTR protein as a critical residue within a binding site for a protein kinase. The localisation of CK2 defines and regulates its metabolic targets; CFTR localises CK2 at the apical membrane of respiratory epithelium and its loss in CF impacts on multiple regulatory pathways that are unrelated to ion transport. I have recently found that the inflammatory phenotype that is so debilitating in CF disease may be dependent upon this CK2 localisation by CFTR.

Prior to the CK2 studies, I investigated other CFTR-associated proteins and discovered that nucleoside diphosphate kinase (NDPK) is associated with AMP-activated protein kinase (AMPK). AMPK and NDPK are mutually regulatory and this relationship is disrupted in CF. I also found a novel association between CFTR and the IgG molecule which led to the funding of a two-year Wellcome Trust grant.

My PhD initially focused on neuronal structural proteins, specifically the identification of the ankyrin-binding integral membrane protein analogous to erythrocyte Band 3 in the membrane-associated cytoskeleton. The project diversified to include the identification of a role for the microtubule-binding protein, MAP2, in synaptic plasticity.

Publications

Maintained by: H Murphie.

The University of Dundee is a Scottish Registered Charity, No.SC015096

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Page last updated: Wednesday 23 April 2008 12:15 PM