Associate Professor Michal Kolář from UCT Prague, together with Klára Hlouchová’s team from Charles University, is turning back the clock four billion years in a project supported by the Czech Science Foundation (GAČR) to investigate the origin of one of life’s key structures – the ribosome. Through a combination of computational and experimental approaches, they aim to uncover the chemical conditions that enabled the formation of its predecessor, the so-called protorribosome. Why is answering this fundamental question important? It might even help us understand the origins of antibiotic resistance.
How would you describe your project to a layperson in a few sentences? Why it is important?
Together with Klára Hlouchová’s team at Charles University, we will study the behaviour of biomolecules under the conditions that existed on Earth before the emergence of life, that is about 4 billion years ago. Specifically, we will focus on the precursor of ribosomes, so-called protoribosomes. I recently spoke about this topic in an interview on the UCT Prague website in connection with our previous research.
What inspired you to choose this topic? Was it a specific challenge you wanted to address, or a kind of natural continuation of your previous work?
My group has been studying ribosomes, cellular protein factories, for a long time, while Klara’s group has been studying the origin of life. Since we enjoy working together, we brought our topics together in one project.
What is the main goal of your research?
We would like to answer the question of what role certain conditions—specifically the concentration of Mg2+ ions, pH, and the presence of peptides—played in the formation of protoribosomes.
What do you think captured the selection committee’s attention the most?
I have already had the opportunity to see the reviewers’ comments. The two main positive aspects of our proposal, according to the reviewers, were the combination of high-quality calculations with a high-quality experimental research plan and an interesting avenue of scientific inquiry.
Will the project lead to any specific applications or technologies?
In the short term, probably not, because we are focusing on fundamental questions about the origin of life on Earth. In the long term, who knows? We are studying the precursor of the modern ribosome, in recent times targeted by a large number of antibiotics. Our knowledge of ribosome abiogenesis may, for example, lead to new approaches in solving antibiotic resistance.
What makes your project unique?
We plan to approach our research question from multiple angles and use both theoretical and experimental methods.
What obstacles or challenges do you anticipate during the project? Do you already have strategies for overcoming them?
We will study early complexes of peptides and RNA, which are small (but conformationally very dynamic) biomolecular systems. The considerable dynamics possess challenges in the structural characterization of the complexes. However, in combination with computer simulations, we might be able to overcome the problem.
What brings you the most joy in working on this project?
My group, with this project, will be investigating something different from ribosomes, which I have been studying for almost ten years. I am looking forward to seeing what these uncharted waters will bring to me.
What, theoretically, should happen with your research after the project is completed?
As is the case with basic research, once you answer one question, ten new questions emerge. So, after the project is over, I'll pick the best one and move forward with it.
Graphic labels (L-R):
Separate building blocks | Simple polymers | Simple condensation | Complex condensation
A scheme of biophysical and biochemical optimization leading to the modern ribosom[A11] e. The green box highlights where our research goals are situated.
A) Isolated biomolecular building blocks (black) and metal ions (yellow).
B) Simple RNAs (light blue) and short peptides (dark blue) occasionally participate in interactions.
C) Simple condensates of longer RNAs and peptides, stabilized by metal ions, increase the catalytic efficiency of the complexes, thereby promoting a positive feedback loop for the synthesis of even longer RNAs and peptides.
D) Complex condensates and the beginning of template synthesis, in which some interactions with metal ions are replaced by direct interactions with better optimized biomolecules.
E) Modern ribosome composed of a large (blue) and a small (red) subunit.