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Cambridge Reproduction


We are interested in all aspects of gene regulation by non-coding RNA. Current research themes include: miRNA biology and pathology, miRNA mechanism, piRNA biology and the germline, endo-siRNAs in epigenetic inheritance and evironmental conditioning, small RNA evolution and the role of RNAi in host pathogen interaction.

piRNA biology and germline genome stability 

piRNAs are animal-specific small RNAs usually restricted to the germline and required for fertility. In 2008 we identified the piRNAs of C. elegans. We have demonstrated that Piwi proteins and piRNAs are important for gemline development and fertility. In the absence of piRNAs germline genome integrity is compromised and consequently piRNAs have been called “guardians of the genome”. Now we are investigating how piRNAs are generated in the germline and how they act to silence their targets. We are also working hard to understand how the piRNA pathway responds to foreign DNA/RNA and how the pathway is evolving.

Selected publications:

Weng C, Kosalka J, Berkyurek AC, Stempor P, Feng X, Mao H, Zeng C, Li WJ, Yan YH, Dong MQ, Morero NR, Zuliani C, Barabas O, Ahringer J, Guang S, Miska EA (2019) The USTC co-opts an ancient machinery to drive piRNA transcription in C. elegans. Genes Dev.

Multigenerational epigenetic inheritance and paramutation

Since August Weismann (1834-1914) formulated the distinction between innate and acquired characteristics at the end of the 19th century, the debate relating to the inheritance of acquired traits has raised many controversies in the scientific community. Following convincing arguments against (e.g. William Bateson) this debate was then set aside by the majority of the scientific community. However, a number of epigenetic phenomena involving RNA, histone modification or DNA methylation in many organisms have renewed interest in this area. Transgenerational effects likely have wide-ranging implications for human health, biological adaptation and evolution, however their mechanism and biology remain poorly understood. We recently demonstrated that a germline nuclear small RNA/chromatin pathway can maintain epi-allelic inheritance for many generations in C. elegans. This is a first in animals and related to "paramutation" discovered over 50 years ago in plants. We are currently further characterizing the mechanisms of paramutation in animals. In addition, we are testing the hypothesis that paramutation provides a transgenerational memory of the environment (“Lamarckism”). We are currently exploring related phenomena in mammals.

Selected publications:

Bezler A, Braukmann F, West SM, Duplan A, Conconi R, Schütz F, Gönczy P, Piano F, Gunsalus K, Miska EA, Keller L. (2019) Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment. PLoS Genet.

Burton N., Riccio C., Dallaire A., Price J., Jenkins B., Koulman A., Miska E.A., C. elegans heritably adapts to P. vranovensis infection via a mechanism that requires the cysteine synthases cysl-1 and cysl-2 (preprint)

Matsushima W, Brink K, Schroeder J, Miska EA, Gapp K (2019) Mature sperm small-RNA profile in the sparrow: implications for transgenerational effects of age on fitness. Environ Epigenet.

Gapp K, van Steenwyk G, Germain PL, Matsushima W, Rudolph KLM, Manuella F, Roszkowski M, Vernaz G, Ghosh T, Pelczar P, Mansuy IM, Miska EA (2018) Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma. Mol Psychiatry.