The role of non-coding RNA in embryonic development
To really understand embryogenesis and its related diseases it is essential to integrate all levels of gene regulation, i.e. transcriptional control, post-transcriptional mechanisms such as mRNA stability, splicing, and editing, translational control and post-translational modifications. One novel regulatory mechanism is the regulation of gene expression by non-coding RNAs (ncRNAs).
Eukaryotic transcriptome analyses have revealed the presence of a huge number of non-coding RNAs (ncRNAs) with developmentally regulated expression, but little is known about their function. This project will address the genetic mechanisms of these ncRNAs using the differentiation of the bipotential gonad into either testis or ovary as a model system. We are elucidating the function of these non-coding RNAs using a series of in vitro, ex vivo and in vivo studies, integrating cell biology, developmental biology, biochemistry, and mouse genetics.
Prof Paul Thomas, University of Adelaide
Dr Patrick Western, Hudson Institute
Dr Joan Jorgensen, University of Wisconsin-Madison, USA
ARC Future Fellowship: "Towards a new understanding of the reproductive system"
NHMRC project grant: "MicroRNA regulation of sex determination and gonad development"
Group of Eight Australia - Germany Joint Research Cooperation Scheme: "Regulation of Wilms' tumour suppressor 1 expression by non-coding RNAs"
NHMRC Career Development Award level II: "The role of non-coding RNAs in development and disease"
ARC Discovery grant: "A new paradigm of gene regulation - Implications in embryogenesis and disease"
- Wainwright EN, Jorgensen JS, Kim Y, Truong V, Bagheri-Fam S, Davidson T, Svingen T, Fernandez-Valverde SL, McClelland KS, Taft RJ, Harley VR, Koopman P, Wilhelm D. SOX9 regulates microRNAs miR-202-5p/3p expression during mouse testis differentiation. Biol Reprod 2013; 89: 34.
- Rakoczy J*, Fernandez-Valverde SL*, Glazov EA, Wainwright EN, Sato T, Takada S, Combes AN, Korbie DJ, Miller D, Grimmond SM, Little MH, Asahara H, Mattick JS, Taft RJ*, Wilhelm D*. MicroRNAs-140-5p/140-3p modulate Leydig cell numbers in the developing mouse testis. Biol Reprod 2013; 88: 143.
- Mercer TR*, Wilhelm D*, Dinger ME*, Solda G*, Korbie DJ, Glazov EA, Truong V, Schwenke M, Matthaei KI, Saint R, Koopman P, Mattick JS. Expression of distinct RNAs from 3' untranslated regions. Nucl Acid Res 2011; 39: 2293-2403.
- McFarlane L, Svingen T, Braasch I, Koopman P, Schartl M, Wilhelm D. Expansion of the Ago gene family in the teleost clade. Dev Genes Evol 2011; 221: 95-104.
- McFarlane L, Wilhelm D. Non-coding RNA in mammalian sexual development. Sex Dev 2009; 3: 302-316.
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