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Ribozyme rolling circle amplification

Carlsbergfondets internationaliseringsstipendier

What

I strive to understand what led to the origin of life by investigating how RNA molecules can be allowed to self-copy. Our understanding of life’s development was established by Charles Darwin. Darwinian evolution relies on a link between genotype (genes) and phenotype (function); that link allows the “fittest” to pass on its abilities to the next generations. However, evolution is not restricted to living organisms. In fact, any system or molecule that holds information allowing for its own reproduction, while also catalysing the process, can independently evolve. RNA is found in our cells today and might be the molecule originally making all of this possible. Unfortunately, the original RNA molecules able to self-copy seems to have been lost over time. I ask, can they be rediscovered?

Why

By investigating the interphase between chemical reactions and evolution, I aim to understand the conditions needed early on in the development of life. This might be used to address questions of how probable origin of life is. Did it happen multiple times and could it happen in other places of the universe? Was the origin of life unlikely, probable or even inevitable? Additionally, if RNA was indeed the original molecule nature chose in early life, it is a strong indication that more unexplored abilities of RNA molecules remain to be discovered. Indeed, catalytic or other types of active RNA molecules are being developed these years, which have the potential of unravelling novel and even unique solutions to be used in biotechnological or medical settings.

How

I use nature’s own optimization strategy, evolution, to develop and optimise catalytically active RNA molecules, called ribozymes. Similar to DNA, RNA molecules consist of sequences of four different bases. An RNA sequence of just 15 bases allow for more than a billion different molecules. A few of those RNA molecules of unknown sequence might be novel ribozymes able to perform a needed reaction. A technique that allows for selection of specific abilities within a few molecules in a huge population, is called directed evolution. Using techniques including directed evolution, I am working on evolving a ribozyme that is optimised for copying circular RNA templates thus developing ribozyme rolling circle amplification (RCA). RCA is potentially needed for efficient RNA-based self-copying.

SSR

Good science addresses the big questions and problems we are faced with and aims to expand our perception of the world we live in. This project can be part of answering one of the biggest questions we can ask in science, how life originated. The techniques applied in this project are not only used in developing ribozymes but also other molecules such as antibodies, which are now beginning to be used as human medicines. Developing our ability to use evolution to optimize a system or develop new types of molecules will bring about new methods to benefit other fields within science and technology as well as the society in general.