Research Interests

My personal research interests vary, and I’ve spent the better part of 10 years of academic research trying to figure out what I’m really most interested in – too many things it turns out. I started graduate school with lab rotations using zebrafish, mice, and fruit flies as model organisms. Eventually, I completed my Ph.D. in a molecular evolution lab, and then transitioned to studying mammalian cells and developmental epigenetics as a postdoctoral research associate. So where to now? I’m not sure where I’ll end up, but I know that I am curious about many avenues of biology, especially those that intersect with health and the public.  My next move will likely be to the biopharmaceutical industry, where I can explore the business of helping improve people’s lives. Please continue reading below to find out more about my previous research.

Research at the University of Oxford

My Postdoctoral project

By studying heterochromatin proteins like LHR and HP1 during my Ph.D., I became fascinated with heterochromatin and wanted to continue to investigate this intriguing way to package DNA. The inactive X chromosome in mammals is a well-studied, unique example of heterochromatin formation, so I naturally turned to this system. My research was focused on studying the protein SMCHD1, which is required for the maintenance phase of X inactivation, as well as other functions in the cell such as DNA repair and gene silencing. Using a combination of biochemical and molecular techniques, I was able to reveal several fundamental properties of this complicated protein. We hope to continue this work, especially those avenues toward the development of therapeutics for the muscular dystrophy disease FSHD.

The Brockdorff Lab

Work in the lab is focused on understanding the molecular mechanism of X chromosome inactivation, the process mammals use to equalise levels of expression of genes on the X chromosome in females relative to males. X inactivation is initiated by expression of a non-coding RNA, Xist, that coats the chromosome from which it is transcribed, bringing about chromatin modifications that in turn lead to heritable gene silencing. We are interested in how X inactivation is regulated in early development, how X chromosome silencing is established and maintained, and how specific pluripotent lineages can reverse stable silencing of the inactive X.  [Brockdorff Lab Website]

 

Research at Cornell University

My Ph.D Project

For my thesis work, I studied the interactions and properties of the gene Lethal hybrid rescue (Lhr).  We demonstrated that LHR is a chromatin-associated protein, and predominantly localizes to heterochromatin.  By using both genetic and molecular biological approaches, I found that Lhr is closely associated with Heterochromatin Protein 1 (HP1) and also interacts with other heterochromatin proteins (HPs).  I also did some preliminary experiments addressing the role of many of these HPs in the hybrid lethal function of Lhr.  Additionally, we discovered that many of the properties including heterochromatic localization, protein interactions, and hybrid lethal activity are conserved for other Lhr orthologs.

The Barbash Lab

The Barbash laboratory is interested in understanding the relationship between genomic change and the creation and divergence of species. Much of the current research investigates the evolutionary origins and developmental mechanisms of reproductive isolating mechanisms between species, such as hybrid sterility and lethality. We are currently using diverse approaches including developmental genetics, biochemistry, molecular evolution and population genetics, and comparative genomics to investigate interspecific hybrid lethality in the fruitfly Drosophila. [Barbash Lab Website]

 

Publications

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Brideau, N. J., Coker, H.A., Gendrel, A.-V.G., Siebert, C.A., Bezstarosti, K., Demmers, J., Poot, R.A., Nesterova, T.B., and Brockdorff, N. (2015). Independent Loading Mechanisms Target the Chromosomal Protein SMCHD1 to H3K9me3 Modified Chromatin and the Inactive X Chromosome. Molecular and Cellular Biology. 2015 Dec 1;35(23):4053-68. [Article]

Satyaki, P.R., Cuykendall, T.N., Wei, K.H., Brideau, N.J., Kwak, H., Aruna, S., Ferree, P.M., Ji, S., Barbash, D.A. (2014). The Hmr and Lhr Hybrid Incompatibility Genes Suppress a Broad Range of Heterochromatic Repeats. PLOS Genetics, Mar 20; 10(3):e1004240 [pdf] [Article]

Brideau, N.J., Barbash, D.A. (2011). Functional conservation of the Drosophila hybrid incompatibility gene Lhr. BMC Evolutionary Biology 11:57. [pdf] [Article]

Brideau, N.J.*, Flores, H.A.*, Wang, J.*, et al. (2006). Two Dobzhansky-Muller genes interact to cause hybrid lethality in Drosophila. Science, 314, 1292-5. [pdf] [Article]

Other articles in Nature, Science 1, 2 and Current Biology about our paper.

Whitlock KE, Illing N, Brideau NJ, Smith KM, Twomey S. (2006). Development of GnRH cells: setting the stage for puberty. Molecular and Cellular Endocrinology, 254-255, 39-50. [pdf] [Article]

 

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