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

Journal Articles

Widagdo J., Zhao Q.Y., Kempen M.J., Chau Y.Q., Spadaro P.A., Ratnu V.S., Edson J., Anggono V. and Bredy T.W. (2016). Experience-dependent accumulation of N6-methyladenosine in the prefrontal cortex is associated with memory processes in mice. Journal of Neuroscience, 36(25), 6771-7.

Pang T., Short A., Fennell K., Perreau V.M., Fox A., O'Bryan M., Kim J.H., Bredy T.W., Hannan A.J. (2016). Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring. Translational Psychiatry, 6(6):e837.

Bjørge M.D., Hildrestrand G.A., Scheffler K., Suganthan R., Rolseth V., Kuśnierczyk A., Rowe A.D., Vågbø C.B., Vetlesen S., Eide L., Slupphaug G., Nakabeppu Y., Bredy T.W., Klungland A. and Bjørås M. (2015). Synergistic actions of Ogg1 and Mutyh DNA glycosylases modulate anxiety-like behavior in mice. Cell Reports, 13(12), 2671-8.

Baker-Andresen D., Zhao Q.Y., Li X., Jupp B., Chesworth R., Lawrence A.J. and Bredy T.W. (2015). Persistent variations in neuron-specific DNA methylation following cocaine self-administration and protracted abstinence in mice. Neuroepigenetics, doi:10.1016/j.nepig.2015. 10.001

Spadaro P.A., Flavell C.R., Widagdo J., Ratnu V.S., Troup M., Ragan C., Mattick J.S. and Bredy T.W. (2015). Long noncoding RNA-directed epigenetic regulation of gene expression is associated with anxiety-like behavior in mice. Biological Psychiatry, doi.j.biopsych.2015.02.004

Ratnu V., Wei W. and Bredy T.W. (2014). Activation-induced cytidine deaminase regulates activity-dependent BDNF expression in post-mitotic cortical neurons. European Journal of Neuroscience, 40, 3032-9.

Li X., Baker-Andresen D., Zhao Q., Marshall V. and Bredy T.W. (2014). MBD ultra-sequencing: a novel method for identifying inter-individual and cell-type-specific variation in DNA methylation. Genes, Brain and Behaviour, 13, 721-31.

Li X., Wei W., Zhao Q., Widagdo J., Baker-Andresen D., Flavell C.R., D’Alessio A., Zhang Y. and Bredy T.W. (2014). Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation. Proceedings of the National Academy of Sciences, 111, 7120-5. (*Faculty of 1000 recommended*)

Fenton G.E., Pollard A.K., Halliday D.M., Mason R., Bredy T.W. and Stevenson C.W. (2014). Persistent prelimbic cortex activity contributes to enhanced learned fear expression in females. Learning and Memory, 21, 55-60.

Barry G., Briggs J.A., Vanichkina D.P., Poth E.M., Beveridge N.J., Ratnu V.S., Nayler S.P., Nones K., Hu J., Bredy T.W., Nakagawa S., Rigo F., Taft R.J., Cairns M.J., Blackshaw S., Wolvetang E.J. and Mattick J.S. (2014). The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Molecular Psychiatry, 19, 486-94.

Ploense K.L., Kerstetter K.A., Wade M.A., Woodward N.C., Maliniak D., Reyes M., Uchizono R.S., Bredy T.W. and Kippin T.E. (2013). Exposure to histone deacetylase inhibitors during Pavlovian conditioning enhances subsequent cue-induced reinstatement of operant behavior. Behavioural Pharmacology, 24, 164-71.

Baker-Andresen D., Flavell C., Li X. and Bredy T.W. (2013). Activation of BDNF signaling prevents the return of fear in female mice. Learning and Memory, 20, 237-40.

Wei W., Coelho C.M., Marek R., Yan S., Li X., Dudley K.J., Sah P., Kobor M.S. and Bredy T.W. (2012). p300/CBP-associated factor (PCAF) selectively regulates the extinction of conditioned fear. Journal of Neuroscience, 32, 11930-41.

Lin Q., Wei W., Coelho C.M., Boskovic Z., Ratnu V.S., Li X, Dudley K., Kobor M.S., Sun Y.E. and Bredy T.W. (2011). The brain-specific microRNA, miR-128b, regulates the formation of fear extinction memory. Nature Neuroscience, 14, 1115-7. (*Faculty of 1000 recommended*)

Marek R., Coelho C.M., Sullivan R.W., Ratnu, V., Dudley, K., Meyers D., Mukherjee C., Cole P.A., Sah P. and Bredy T.W. (2011). Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300. Journal of Neuroscience, 31, 7486-91.

Reviews and Book Chapters

Nainar S., Marshall P.R., Tyler C.R., Spitale R.C. and Bredy T.W. (2016). Evolving insights into RNA modifications and their functional diversity in the brain, Nature Neuroscience (in press)

Ratnu V.S., Emami M. and Bredy T.W. (2016). Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain. Journal of Neuroscience Research (in press)

Marshall P. and Bredy T.W. (2016). Cognitive neuroepigenetics: the next evolution in our understanding of the molecular mechanisms underlying learning and memory? Science of Learning (in press)

Marshall P. and Bredy T.W. (2016). What does the future hold for the study of nucleic acid modifications in the brain? In: DNA modifications in the brain” (Elsevier) (in press)

Bredy T.W. (2016). DNA modifications in the brain. Editor (Elsevier) (in press)

Alaghband Y., Bredy T.W. and Wood M.A. (2016). The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action. Neuroscience Letters. pii: S0304-3940(16)30022-2. doi: 10.1016/j.neulet.2016.01.023.

Flavell C.R., Lambert E.A., Winters B.D. and Bredy T.W. (2014). Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction. Frontiers in Behavioural Neuroscience, 7, 214.

Li X., Wei W., Ratnu V.S. and Bredy T.W. (2013). On the potential role of active DNA demethylation in establishing epigenetic states associated with neural plasticity and memory. Neurobiology of Learning and Memory, 105,125-32.

Marek R., Strobel C., Bredy T.W. and Sah P. (2013). The amygdala and medial prefrontal cortex: partners in the fear circuit. Journal of Physiology, 591, 2381-91.

Baker-Andresen D., Ratnu V.S. and Bredy, T.W. (2013). Dynamic DNA methylation: a prime candidate for genomic metaplasticity and behavioral adaptation. Trends in Neurosciences, 36, 3-13.