Genetic technologies in neuroscience

In vitro, in cell culture and in silico

We use in vitro assays and cell culture (e.g. insect S2 cells, rodent primary neurons and glia) to investigate protein function, gene structure, expression, regulation and epigenetics (e.g. including genetic linkage, DNA damage, RNA biology, non-coding RNA), using molecular biology methods (e.g. CRISPR/Cas9) and omics (e.g. genomics, transcriptomics, proteomics) approaches with bioinformatics and computational approaches to investigate how genetic information contributes to brain function.

Model organisms such as fruit-flies and rodents

These are used to investigate genetic, molecular, cellular and neural circuit mechanisms of nervous system structure and function, in development and throughout the life-course, in organ cultures, in vivo and in time-lapse. Using the fruit-fly Drosophila and mice, classical and cutting-edge genetics are used to trace genes throughout the generations in order to create genetic combinations that enable the investigation of how distinct cell types interact (e.g. neurons and glia; neurons with each other to build neural circuits) and how genes influence such interactions. Using genetics in fruit-flies and mice, genes can be switched on or off, constantly or at specific time points, ubiquitously or in specific cell types, to investigate what genes do; thermo- and opto-genetics are used to switch neurons on or off; reporters are used to visualise neurons and glia in action in vivo; genetic connectivity tools are used to test connectivity between neurons within neural circuits; and behavioural assays are used in freely moving animals to test circuit function. Using these model organisms, our research includes investigating neural development, cellular molecular mechanisms of tissue homeostasis and dysregulation in cell death and cancer; how neural circuits change throughout the life-course and in response to experience, through structural plasticity and degeneration; how neural circuits create behaviour and the circuit mechanisms of decision making; mechanisms underlying dementias and other brain diseases; and whether genetic manipulations can facilitate regeneration after spinal cord injury and traumatic brain injury in rodents and their equivalent in fruit-flies.

Research in humans

Genome Wide Association Studies (GWAS) have revealed genes linked to brain diseases and disorders in humans. Genetic approaches can now be used to investigate what genes do using a combination of in vitro, cell culture, in vivo work using model organisms, brain imaging in human volunteers and patients and further research using donated tissues. In humans, we also use neurogenetics to investigate cognitive neuropsychology, psychiatry, epidemiology and carry out clinical trials. 

Data science: Our work uses approaches including multimodal large data harmonization, Artificial Intelligence and Machine Learning, and multimodal integrative analytics to build mechanistic models to advance understanding of genetic and environmental contributions to various behavioural states and clinical conditions. Particular foci include age-related cognitive decline, antisocial, aggressive and impulsive behaviour, movement disorders and psychotic illness.