LABORATORY OF NON-CANONICAL MODES OF INHERITANCE
@ The Rockefeller University
I. HOW DO PIWI/piRNAs LIMIT SELF-PROPAGATING HERITABLE SMALL RNAs?
Wahba’s postdoc work found that some heritable small RNAs propagate through self-perpetuating amplification cycles, a strategy that allows for the indefinite spread of silencing signals across generations--but risks overamplifying them. To limit the potentially dire consequences of sRNA overamplification, Wahba discovered that the piRNA pathway (involving a second type of Argonaute/sRNA ribonucleoprotein) acts as an essential negative modulator. In the absence of piRNAs, worms progressively lose fertility over multiple generations until they become completely sterile, the result of genes targeted by endogenous Argonautes/small RNAs succumbing to perpetual and inappropriate transgenerational silencing. We aim to mechanistically understand how PIWI/piRNAs contribute to the regulation of heritable silencing.
II. WHAT DRIVES CONSERVATION/DIVERSITY OF NONGENETIC INHERITANCE?
While features of genetic inheritance are widely conserved, nongenetic inheritance mechanisms have been subject to recurrent phylogenetic and operational diversification. Through comparative genomics and studying nongenetic inheritance across species we hope to understand generalizable principles of conservation and diversity in the regulation of nongenetic inheritance.
III. (HOW) DOES NONGENETIC INHERITANCE INFLUENCE EVOLUTION?
The extent to which nongenetic inheritance contributes to evolution remains an open question, and few experimental setups exist to study the process. In our lab we are actively working on experimental setups that will allow us to dissect the inheritance of nongenetic information, its potential impact on genetic inheritance and whether mechanisms that actively oppose the conversion of nongenetic changes to more permanent (genetic) ones exist.