Basic Science: in-vitro and in-vivo models

Testing possibilities through in-vitro and in-vivo models

Many mental disorders lack the clear singular pathophysiological targets that allow focussed treatment discovery that happens in other areas of medicine. Consequently, for mental health, traditional drug discovery efforts have slowed and yielded few successes in recent decades.

But rather than starting at the source, can we reverse-engineer our way to new medication or lifestyle possibilities? The Basic Science team uses biology, molecular biology, drug repurposing, and biomarker discovery to map how known treatments change patterns of gene expression, to understand more about the otherwise-opaque pathways that yield their effect. An innovative stem cell based pre-clinical drug discovery model, pioneered by Prof. Ken Walder and his team, is one piece of the armoury. Focussed initially on bipolar disorder, we have begun expanding this promising model out to look at other conditions, too.

Prof Walder has developed an innovative preclinical drug discovery model that bypasses the lack of a clear pathophysiological target in many disorders by reverse-engineering the effects of combinations of known treatments in terms of their effects on gene expression. This work initially focused on bipolar disorder, and we have begun expanding this promising model to schizophrenia – a next step that CREDIT would facilitate. Notably, our work using this model examines the net effects of combinations of molecularly and mechanistically different agents (lithium, quetiapine, lamotrigine, and valproate) that share therapeutic benefits in a given disorder (bipolar disorder), to avoid merely detecting similar agents rather than novel therapeutics.

This theme spans cell biology, molecular biology, drug repurposing, and biomarker discovery through three major programs:

Bipolar disorders stem cell project

We collect blood samples from patients with bipolar disorder and healthy, matched controls. We then look for differences between the patients and controls for factors such as their mitochondrial function, oxidative stress and inflammation. We then screen drug libraries to see if there are possible drugs we could repurpose to treat bipolar disorder and other disorders.

Myalgic encephalomyelitis/ chronic fatigue syndrome project

We use a similar process to the above project. but with ME/CFS patients. ME/CFS is a complex and disabling disease that affects many parts of the body, including the brain and muscles, as well as the digestive, immune and cardiac systems, among others.

Biomarker program

Working with a range of clinical researchers across Australia, we measure a range of circulating factors in plasma/serum samples and analyse whether these can predict treatment response of patients in clinical trials.