Institute of Neuroscience

Staff Profile

Dr David Koss

Research Associate

Background

My research centres on the biological processes which underlie neurodegenerative dementias, specifically those associated with Lewy body dementia and Alzheimer’s disease.  I am particularly fascinated by the emergence and production of pathological tau, β-amyloid and α-synuclein conformers. These misfolded monomers, oligomers and fibrils are formed as a consequence of the protienopathy associated with dementias and may represent the key to disease modifying treatments. Over the last decade, it has become apparent that the large pathological aggregates (neurofibrillary tangles, senile plaques and Lewy bodies) associated with these diseases do not account for much of the damage observed in the brain. Furthermore clear relationships of aggregate burden and disease severity have failed to be established. Thus in order to better identify causative molecular agents within these diseases we require to investigate a greater range of toxic protein conformers of which a spectrum of assemblies is beginning to emerge. I believe that by understanding the heterogeneous population of toxins which exist in pathological conditions we may be able to identify novel disease relevant molecular targets in order to inform future clinical interventions.

The consequences of impaired cellular homeostasis as a result of tau, β-amyloid and α-synuclein insults which include the dysregulation of calcium signalling homeostasis and ER stress are of equal interest to me. As such disruptions to cellular processes triggered by dementia relevant toxins are likely to instigate the neuronal dysfunction and cell death which give rise to the devastating symptoms of disease. Defining the precise mechanism by which these systems begin to fail may thus highlight essential downstream targets for therapeutics.

Having joined the Newcastle based Laboratory of Prof Tiago Outeiro in July of 2018, I am currently applying my research skills and background to focus on synucleinopathies. Here, in close collaboration with the research team of Prof Johannes Attems, we seek utilise both research models and post-mortem human tissue to bridge the divide between experimental systems and human diseases and improve the translational value of research outcomes.  

Publications