Non-Mendelian genetics & Transgenerational epigenetic inheritance

Revolutionary discoveries in molecular biology, published in recent years, are making the once heretic idea of inheritance of acquired traits relevant again. Parental experiences, at least in worms, can affect the progeny’s physiology, sometimes permanently, or at least for multiple generations. In C.elegans, the mechanisms are being revealed, and the rate of progress is truly exciting. We are interested in inheritance of small RNAs, molecules that are actively shuttled between different tissues, and from the soma to the germline. We discovered that small RNAs are transcribed in response to different environmental stresses (Cell 2011, Cell 2014). We showed for the first time that heritable small RNAs are not diluted, since RNA-dependent RNA polymerases amplify the response in the progeny, in every generation (Cell 2011). Moreover, we recently discovered that a systemic feed back mechanism determines whether to “memorize the epigenetic response” (continue and transmit the ancestral information to additional generations), or whether to terminate the response, “forget” the memory, and rely once again on the hardwired genetic program (Cell 2016, Current biology 2017).

We were the first to show (Genes & Development, 2009) that functional small RNAs can move between interacting human cells (through the immunological synapse). We are motivated to discover whether the principles that govern epigenetic inheritance in C.elegans hold true also to mammals.    

Molecular mechanisms for encoding of memory

We are interested in how information is represented in the nervous system, and how “the code” is implemented to produce behavior. In the broadest sense of the word, memory is what enables altering of future responses based on history. Many types of molecular mechanisms can retain memories in biological systems, for example, metabolic differences, epigenetic factors, stable bioelectrical circuit modes, or neuronal-circuits. We are studying how C.elegans, Planaria, and songbirds encode different types of memories. We are collaborating with computational neuroscientists, economists and linguists, trying to bridge the gaps between the type of neuroscience that is typically conducted by cognitive scientists, and the type of neuroscience that is typically studied by molecular biologists and geneticists. Specifically in C.elegans, since neuronal connectivity is largely hardwired and innate, it is very tempting to speculate that learning and memory are achieved by epigenetic mechanisms (or in the broad sense, mechanisms of gene regulation).

 

Evolution

Evolution depends on variability and selection (and drift) . According to the classic interpretation of the “Modern synthesis” between Mendel, Darwin and the principles of population genetics, the environment enforces selection, but doesn’t affect variability. However, numerous epigenetic mechanisms that enable the environment to affect heritable variations are now known. We are studying whether and how epigenetic information can establish transient and stable variations, and as a consequence alter the rates of evolutionary processes. Moreover, since epigenetic effects can in theory allow adaptive changes in progeny, in response to parental reactions to environmental challenges, epigenetic inheritance has the potential ability to direct evolution’s path. To study these questions we are performing lab evolution experiments in a number of different model organisms, and record evolutionary processes as they take place.