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Intersection of Genetics, Epigenetics, and Environmental Factors in Neural Development and Function

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

The MacDonald Lab, located in the Department of Biology and Program in Neuroscience at Syracuse University, is broadly interested in understanding how the brain develops, and alterations that occur in neurodevelopmental or neuropsychiatric disorders. In particular, we focus on the neocortex, the area of the brain responsible for much of the high-level cognitive processing, and we are working to unravel how genetic factors and environmental factors intersect to orchestrate the development of this important brain region.

The molecular and cellular mechanisms that mediate interactions between genetic and environmental factors are poorly understood. To tackle this complex biology, we study how environmental factors and nutrition (e.g. vitamin D, folic acid, high-fat diet) modify neuronal development and function in both normal mice and mice with genetic mutations that model neuronal disruptions in human neurological disorders. We are particularly interested in epigenetic factors since the epigenome sits at the interface between genes and the environment, and disruptions in epigenetic regulation lead to numerous disruptions in neuronal development and function. Two of our current projects focus on genetic mutations in epigenetic regulators – Mecp2, mutations in which lead to the severe neurological disorder Rett syndrome, and Cited2, mutations in which lead to neural tube closure defects and disrupted neocortical development.

We examine these intersections at multiple stages of development, from embryonic progenitors through to axonal and dendritic connectivity of mature neurons. We use a broad range of experimental approaches, including transcriptome (RNA-seq) and epigenome (Methyl-Seq) analyses on purified neuron subpopulations, in vitro models, molecular and biochemical approaches, immunohistochemistry, analysis of neuronal morphology with Golgi staining, in utero electroporation, and axonal tracing.

We are currently looking for PhD students with a strong interest and background in Neuroscience and/or Epigenetics. For more information on our research, please visit our lab website at: https://jemacdon.expressions.syr.edu/

Students must apply to the Department of Biology PhD Program. For more information on how to apply to the program, see the Department of Biology Graduate Studies at: http://biology.syr.edu/graduate/apply.html

Students in Cell Biology, Developmental Biology, Genetics, and Neuroscience rotate in 2-3 labs in the first year and then choose one for their PhD. For a list of other Developmental Biology and Neuroscience labs at Syracuse University, see http://biology.syr.edu/research/research.html

Funding Notes

Application Deadline: Until December 15th 2017, we will be accepting applications for a start date of end of August 2018. After this we will be starting to accept applications for a start date of end of August 2019. Funding is provided through a combination of research and teaching assistantships and is guaranteed for 5 years (dependent on satisfactory progress).

References

Fame, R.M.* & MacDonald, J.L.*, Dunwoodie, S.L., Takahashi, E., and Macklis, J.D. (2016) Cited2 regulates neocortical layer II/III generation and somatosensory callosal projection neuron development and connectivity. Journal of Neuroscience. 36(24):6403-6419 (with cover) *Co-first authors

Kishi, N.* & MacDonald, J.L.*, Ye, J., Molyneaux, B.J., Azim, E., and Macklis, J.D. (2016) Reduction of aberrant NF-kB signalling ameliorates Rett Syndrome phenotypes in Mecp2-null mice. Nature Communications. 7:10520 *Co-first authors

MacDonald, J.L.* & Fame, R.M.*, Azim, E., Shnider, S.J., Molyneaux, B.J., Arlotta, P., and Macklis, J.D. (2013) Specification of cortical projection neurons: transcriptional mechanisms. Comprehensive Developmental Neuroscience: Patterning and Cell Type Specification in the Developing CNS and PNS. Vol.1:475-502. Editors J.L.R Rubenstein and P. Rakic. Elsevier. *Co-first authors

Fame, R.M.* & MacDonald, J.L.*, and Macklis, J.D. (2011) Development, specification, and diversity of callosal projection neurons. Trends in Neurosciences. 34(1):41-50. *Co-first authors

MacDonald, J.L., Berndt, A., Verster, A., and Roskams, A.J. (2010) MBD2 and MeCP2 regulate distinct transitions in the stage-specific differentiation of olfactory receptor neurons. Molecular and Cellular Neuroscience. 44:55-67

Molyneaux, B.J.*, Arlotta, P.*, Fame, R.M. †, MacDonald, J.L. †, MacQuarrie, K.L., and Macklis, J.D. (2009) Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons. Journal of Neuroscience. 29(39):12343-54 (with cover) *Co-first authors; †Co-second authors

MacDonald, J.L. and Roskams, A.J. (2009) Epigenetic regulation of nervous system development by DNA methylation and histone deacetylation. Progress in Neurobiology. 88(3):170-83

MacDonald, J.L. and Roskams, A.J. (2008) Histone Deacetylases 1 and 2 are expressed at distinct stages of neuro-glial development. Developmental Dynamics. 237(8):2256-2267

MacDonald, J.L., Gin, C., and Roskams, A.J. (2005) Stage-specific induction of DNA methyltransferases in olfactory receptor neuron development. Developmental Biology. 288(2):461-73

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