Dr Timothy Bredy

Contact Information

t.bredy@uq.edu.au
Building: QBI Building #79
Room: 626
Tel: +61 7 334 66391

Mailing Address

Queensland Brain Institute
The University of Queensland
Brisbane, 4072
Queensland,
Australia

Links

Lab Members

Lab Home Page

Short biography

Research directions

Current collaborations

Selected publications

 

Short biography

Originally from Halifax, Canada, I completed a B.Sc. (Hon) in Experimental Psychology with Dr Richard Brown at Dalhousie University. In 1999, I moved to Montreal to work with Dr Michael Meaney and, in 2004, earned a Ph.D. in Neurological Sciences from McGill University. For my thesis, I examined gene-environment interactions and the influence of early life experience on cognitive development. From 2005 through 2009, I was awarded FRSQ, NSERC and CIHR research fellowships to pursue postdoctoral training at the University of California (Los Angeles). I worked with two very talented researchers at UCLA: Dr Mark Barad, a psychiatrist with significant expertise in fear-related anxiety disorders and their treatment, and Dr Yi Sun, a leader in the emerging field of epigenetics and stem cell biology. During my time at UCLA, I initiated collaboration for cross-disciplinary studies in epigenetics with Dr Michael Kobor at the University of British Columbia, and studies in drug addiction with Dr Tod Kippin at UCSB. In August 2009, I established the Psychiatric Epigenomics Laboratory at QBI.

 

Research directions

The main aim of our research is to understand how epigenetic mechanisms contribute to the formation and maintenance of long-term memories, particularly within the context of psychiatric disorders such as phobia, post-traumatic stress disorder (PTSD), and the addictions. More generally speaking, we are interested in elucidating how the genome is connected to the environment, and how this relationship shapes brain and behaviour across the lifespan. Embedded within the chromatin environment, directly at the interface between intracellular signaling and DNA within the nucleosome, epigenetic mechanisms including histone modifications, DNA methylation and non-coding RNA’s represent an attractive foundation for experience-dependent, long-lasting changes in gene expression, cellular function and behaviour. In contrast to the information conveyed by a static genome, the epigenome is very dynamic and can be modified by exposure to a variety of environmental stimuli including a variety of learning paradigms, exposure to drugs of abuse, environmental toxins, dietary factors, and social interaction. For example, we have recently discovered that fear-related learning is associated with epigenetic modification of genes within the prefrontal cortex. The acquisition and extinction of conditioned fear lead to distinct patterns of histone acetylation around the P4 promoter of the gene encoding brain-derived neurotrophic factor (BDNF) (Bredy et al., 2007). We have also shown that histone deacetylase (HDAC) inhibitors, when administered during spaced extinction training, enhance long-term extinction memory and prevent renewal of conditioned fear (Bredy et al., 2008), evidence which suggests that the epigenome may represent a therapeutic epigenomic point of intervention for the treatment of fear-related anxiety disorders.

Current Collaborations

  • Professor John Mattick, Institute for Molecular Bioscience, The University of Queensland
  • Professor Andrew Lawrence, Howard Florey Institute
  • Associate Professor Tod Kippin, University of California (Santa Barbara)

Selected publications

Activation-induced cytidine deaminase regulates activity-dependent BDNF expression in post-mitotic cortical neurons. Ratnu VS, Wei W, Bredy TW. Eur J Neurosci. 2014 Oct;40(7):3032-9.

Methyl CpG binding domain ultra-sequencing: a novel method for identifying inter-individual and cell-type-specific variation in DNA methylation. Li X, Baker-Andresen D, Zhao Q, Marshall V, Bredy TW. Genes Brain Behav. 2014 Sep;13(7):721-31.

Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation. Li X, Wei W, Zhao QY, Widagdo J, Baker-Andresen D, Flavell CR, D'Alessio A, Zhang Y, Bredy TW. Proc Natl Acad Sci U S A. 2014 May 13;111(19):7120-5.

On the potential role of active DNA demethylation in establishing epigenetic states associated with neural plasticity and memory. Li X, Wei W, Ratnu VS, Bredy TW. Neurobiol Learn Mem. 2013 Oct;105:125-32

Dynamic DNA methylation: a prime candidate for genomic metaplasticity and behavioral adaptation. Baker-Andresen D, Ratnu VS, Bredy TW. Trends Neurosci. 2013 Jan;36(1):3-13.

p300/CBP-associated factor selectively regulates the extinction of conditioned fear. Wei W, Coelho CM, Li X, Marek R, Yan S, Anderson S, Meyers D, Mukherjee C, Sbardella G, Castellano S, Milite C, Rotili D, Mai A, Cole PA, Sah P, Kobor MS, Bredy TW. J Neurosci. 2012 Aug 29;32(35):11930-41.

Dynamic DNA methylation: a prime candidate for genomic metaplasticity and behavioral adaptation. Baker-Andresen D, Ratnu VS, Bredy TW. Trends Neurosci. 2012 Oct 4.

p300/CBP-associated factor selectively regulates the extinction of conditioned fear. Wei W, Coelho CM, Li X, Marek R, Yan S, Anderson S, Meyers D, Mukherjee C, Sbardella G, Castellano S, Milite C, Rotili D, Mai A, Cole PA, Sah P, Kobor MS, Bredy TW. J Neurosci. 2012 Aug 29;32(35):11930-41.

Emerging role of non-coding RNA in neural plasticity, cognitive function, and neuropsychiatric disorders. Spadaro PA, Bredy TW. Front Genet. 2012;3:132.

The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory. Lin Q, Wei W, Coelho CM, Li X, Baker-Andresen D, Dudley K, Ratnu VS, Boskovic Z, Kobor MS, Sun YE, Bredy TW. Nat Neurosci. 2011 Aug 14;14(9):1115-7.

Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300. Marek R, Coelho CM, Sullivan RK, Baker-Andresen D, Li X, Ratnu V, Dudley KJ, Meyers D, Mukherjee C, Cole PA, Sah P, Bredy TW. J Neurosci. 2011 May 18;31(20):7486-91.

MicroRNA regulation of neural plasticity and memory. Bredy TW, Lin Q, Wei W, Baker-Andresen D, Mattick JS. Neurobiol Learn Mem. 2011 Jul;96(1):89-94.

Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders. Dudley KJ, Li X, Kobor MS, Kippin TE, Bredy TW. Neurosci Biobehav Rev. 2011 Jun;35(7):1544-51.

How the epigenome contributes to the development of psychiatric disorders. Bredy TW, Sun YE, Kobor MS. Dev Psychobiol. 2010 May;52(4):331-42. Review.