Epigenetics and Neural Plasticity Group
Our group investigates gene-environment interactions and experience-dependent plasticity in the healthy and diseased brain. We explore how genetic and environmental factors combine to influence predisposition to specific brain disorders, both within and between generations.
About our research
Our work on pre-clinical models of brain disorders includes Huntington’s disease (with a focus on psychiatric symptoms and dementia), schizophrenia, autism, depression and anxiety disorders. While these conditions have diverse genetic components, they share common environmental influences that impact risk and resilience, such as exercise, diet, stress, cognitive stimulation and infection.
We also explore epigenetic inheritance, investigating how specific environmental factors can alter paternal epigenetic information in sperm, thus affecting offspring brain development and function. Our findings highlight the importance of understanding how gene-environment interactions shape cognitive, emotional and behavioural functions.
Our research delves into brain-body interactions, including the gut microbiome and the microbiota-gut-brain axis. We have discovered the first evidence that the gut microbiome, and the microbiota-gut-brain axis, is altered in Huntington’s disease. Additionally, we’ve discovered changes to the microbiota-gut-brain axis in a pre-clinical model of schizophrenia. We also examine how other biological systems, like the immune system, interact with the brain, shedding light on how infections (e.g. COVID-19) may influence susceptibility to specific neurological and psychiatric disorders.
- Huntington’s disease and associated psychiatric symptoms and dementia
- Autism, schizophrenia, depression and anxiety disorders
- Neurofibromatosis (NF1) and associated autism, ADHD and learning difficulties
- Brain plasticity in health and disease
- Genetic and environmental factors causing cognitive and affective disorders
- Epigenetics within and between generations
- Effects of stress, exercise, cognitive stimulation, diet and infection on the brain
- The gut microbiome and microbiota-gut-brain axis in health and disease
- Epigenomic, transcriptomic, proteomic and metabolomic analyses of the brain and other tissues
- Epigenetics including analyses of non-coding RNAs and DNA modifications
- Gene expression analyses, including quantitative real-time PCR, Western analysis and ELISAs
- Histology, immunohistochemistry and unbiased stereology
- Epigenetic inheritance including analyses of sperm and embryo epigenetic modifications
- Gut, microbiome and microbiota-gut-brain axis analyses, including analysis of 16S rRNA amplicon sequencing and metagenomic data
- Bioinformatic analyses epigenetic, transcriptomic, proteomic and metabolomic data
Environmental exposures and experience modifying the onset of Huntington’s disease
Our research includes using a model of Huntington’s disease (HD), a tandem repeat disorder, where we are following up our discoveries regarding the beneficial effects of environmental enrichment (enhanced cognitive stimulation and physical activity) and exercise, as well as depression and dementia-like symptoms associated with abnormalities of brain plasticity. Furthermore, we recently discovered that chronic stress could accelerate the onset of HD, and we are investigating these neurotoxic effects of stress in HD and other brain disorders.
Genetic and environmental factors combining and causing specific brain conditions
Many neurological and psychiatric disorders have their origins in abnormal maturation of the brain, including the billions of neurons exquisitely connected by trillions of synapses. We are also investigating how genetic and environmental factors combine to cause specific disorders of brain development and cognition, including schizophrenia and autism spectrum disorders (ASD). We are interested in the mechanisms whereby specific genes regulate maturation of the brain and are dynamically regulated by interaction with the environment in conditions like ASD and schizophrenia.
Linking cognition with the underlying cellular and molecular mechanisms
Our research links data at behavioural and cognitive levels to underlying cellular and molecular mechanisms. We use a variety of behavioural tools, including automated touchscreen testing of cognition and high-throughput data analysis of vocalisation and communication, that are directly translatable to clinical tests. We are establishing the extent to which experience-dependent plasticity, including adult neurogenesis and synaptic plasticity, can modulate these behavioural and cognitive endophenotypes, in models with targeted genome editing. This cellular level of understanding is linked, in turn, to molecular mechanisms, including epigenetics, transcriptomics, proteomics and metabolomics.
Enviromimetics: a new concept
Based on this research, and the identification of key target molecules, we are also exploring the concept of ‘enviromimetics’, therapeutics that mimic or enhance the beneficial effects of cognitive stimulation and physical exercise. We have recently extended this work to explore a subclass of enviromimetics, ‘exercise mimetics’, which may mimic or enhance the therapeutic impacts of physical activity. One goal is to develop such therapeutic agents to help reduce the personal and societal burdens of devastating brain disorders such as HD, dementia, schizophrenia, depression and anxiety disorders.
‘By understanding how genetic and environmental factors contribute to brain disorders such as Huntington’s disease, dementia, schizophrenia, depression and anxiety disorders, we can help develop new ways to prevent and treat these devastating disorders.’
- Experience-dependent plasticity modulating cognitive deficits in schizophrenia
- Gene-environment interactions modulating dementia and depression in a tandem repeat disorder
- Identifying and manipulating the neural circuits of decision-making
- The microbiota-gut-brain axis and microbiome modulation in pre-clinical models of psychiatric disorders
- Transgenerational epigenetic inheritance modulating brain function, behaviour and cognition
- Coralina Collar Fernandez
- Riki Dingwall
- Lucas Hoffmann
- Pamudika Kiridena
- Elizabeth Kleeman
- Sydney Lofquist
- Da Lu
- Bethany Masson
- Nicholas van da Garde
- Pranav Adithya
- Mathilda Doran
- Baijia Li
- Wendy Qin
- Qi Meng
- Gubert, C., Choo, J.M., Love, C.J., Kodikara, S., Masson, B.A., Liew, J.J.M., Wang, Y., Kong, G., Narayana, V.K., Renoir, T., Lê Cao, K.A., Rogers, G.B. and Hannan, A.J. (2022). Faecal microbiota transplant ameliorates gut dysbiosis and cognitive deficits in Huntington’s disease mice. Brain Communications, [online] 4(4), p.fcac205. doi:https://doi.org/10.1093/braincomms/fcac205.
- Gubert, C. and Hannan, A.J. (2021). Exercise mimetics: harnessing the therapeutic effects of physical activity. Nature Reviews Drug Discovery, [online] 20(11), pp.862–879. doi:https://doi.org/10.1038/s41573-021-00217-1.
- Hannan, A.J. (2021). Repeat DNA expands our understanding of autism spectrum disorder. Nature, 589(7841), pp.200–202. doi:https://doi.org/10.1038/d41586-020-03658-7.
- Gubert, C., Kong, G., Renoir, T. and Hannan, A.J. (2020). Exercise, diet and stress as modulators of gut microbiota: Implications for neurodegenerative diseases. Neurobiology of Disease, [online] 134, p.104621. doi:https://doi.org/10.1016/j.nbd.2019.104621.
- Kong, G., Cao, K.-A.L., Judd, L.M., Li, S., Renoir, T. and Hannan, A.J. (2020). Microbiome profiling reveals gut dysbiosis in a transgenic mouse model of Huntington’s disease. Neurobiology of Disease, 135, p.104268. doi:https://doi.org/10.1016/j.nbd.2018.09.001.