Using in vitro selection to study the origins of life and to develop RNA tools

Synopsis

The process by which life started on this planet is one of the key unanswered questions of our time. All available biological evidence suggests that RNA played a key role in early evolution, while a panel of chemical and astrophysical data is consistent with RNA being present at the emergence of the very first life. Even today RNA is critical for life: RNA catalysis being essential for protein synthesis, while RNA processing and regulation is important for many types of gene regulation.  Several of these RNA activities being rooted to the last universal ancestor of all current life.  This period of evolution ending several billion years ago, long before the oxygenation of the Earth’s atmosphere. My laboratory has been studying this ‘RNA World’ via the use of in vitro selection. By screening very large populations (>10¹⁵) of RNA molecules for biochemical function we have been studying the catalytic properties of RNA from an evolutionary perspective.  We have been attempting to produce self-evolving RNA systems that could potentially model the very first replicative steps required for life.  Simultaneously we have been developing RNA tools to facilitate the study of RNA-dependent cellular processes.  I will discuss my laboratories recent efforts in these two research areas and the importance of biophysics for both.