In her research, she delves into the origins of life on Earth. What keeps her awake at night are the 20 amino acids that have formed the building blocks of proteins in all organisms since the very beginning—from the simplest life forms to humans. What would life look if the identity of these amino acids changed? Could life even emerge under such circumstances? These are the questions Klára Hlouchová from the Faculty of Science at Charles University aims to answer. Her work has significant implications for synthetic biology and the development of synthetic organisms, which could be used in drug development, among other applications. Thanks to securing a prestigious ERC Consolidator Grant in December, awarded by the European Research Council (ERC) for groundbreaking projects, her team can now advance its research.
What is the focus of the Synthetic Biology Laboratory that you lead at the Faculty of Science?
Our research lies at the intersection of chemistry and biology. Therefore, our laboratory is comprised of experts from various disciplines, but we are united by a shared interest in the fundamental elements of life, particularly proteins, RNA, and DNA.
We explore the basic principles of life—how it could have originated and how the first proteins appeared on Earth. We also investigate the mechanisms through which life can evolve. One of our key questions is whether life could function with slightly different proteins, meaning ones made from different amino acids.
The questions we tackle pertain to life on Earth but also extend to life as a phenomenon, which we may one day discover elsewhere in the universe. We are curious whether life at the molecular level would resemble what we know on Earth or be entirely different.
You mentioned that your team focuses on "how." I’m curious about "why." Why is it important to study how life originated almost four billion years ago?
We want to understand why life is the way it is and whether it could have developed differently. This is the central mission of our laboratory and has potential applications in the field of artificial life or synthetic biology. Today, synthetic cells are being used to produce various drugs and other substances, serving as miniature factories. These could potentially replace chemical synthesis, which is energy-intensive, expensive, and often generates significant waste.
While our primary goal is to explore the limits of life through basic research, we might also contribute to the development of a synthetic cell that is energetically efficient and stripped of all non-essential components. This carries potential practical benefits.
An illustration of prebiotically plausible RNA-protein interaction with assistance of metal ions (author: Valerio G. Giacobelli).
Your team is built on interdisciplinarity. What disciplines are represented among your laboratory members?
The majority of our team consists of molecular biologists and biochemists, but we also have a biotechnologist, a bioinformatician, physicists, and chemists. Our work demands a multidisciplinary approach because the questions we explore sit at the intersection of all these fields. This diversity is something we enjoy, and I think it also appealed to the European Research Council evaluation panel.
ERC-supported projects aim to push the boundaries of human knowledge and have a global impact. What is the unique idea behind your project that earned this support?
The short title of our project is LIFE-19. All life on Earth, from the simplest bacteria to humans and plants, relies on proteins—the basic structural and functional units in cells. Proteins are always made up of 20 amino acids. These amino acids are deeply rooted in the genetic coding system, or the central dogma of biology. Despite the vast diversity of life, this is a shared characteristic.
Our aim is to attempt to reduce these 20 amino acids to 19, eliminating one amino acid from the entire proteome (the set of all proteins) by reprogramming it in the genome to another amino acid. We’re not focused on replacing a specific amino acid with a particular substitute; instead, we will explore various options to find the most viable one. The goal is to create a simple bacterium that only uses 19 amino acids to produce proteins and observe the consequences.
This experiment may fail, and that’s fine too because the core question is whether such a form of life is even feasible. This approach is like traveling back in time—something that can only be done to a certain extent in evolution. We don’t know if we can revert life to such an ancient state. To our knowledge, no one has attempted this on the scale of an entire cell before. Simplifying the cellular apparatus in this way would be a significant step toward creating a synthetic cell that requires less energy to produce proteins, which would be a substantial breakthrough for synthetic biology.
Klára Hlouchová Research Group.
Do you recall the "aha" moment that led to this idea, or did it evolve gradually during your research?
It stems directly from what we’ve been working on over the past years. We devoted significant effort to creating proteins with a reduced set of amino acids. We discovered that some proteins can function with only half of the standard amino acid repertoire while still performing their intended roles.
However, we initially focused on specific proteins that we believed were capable of this due to their size or defined functions. When we saw that it worked in vitro, we naturally began to wonder whether it could work within a living cell.
What will the grant enable you to achieve? Will you expand your team or upgrade your laboratory?
We will need to acquire one or two new pieces of equipment to further outfit our laboratory. Additionally, our team will expand slightly, mainly with another bioinformatician. Most of the funding will go toward genome engineering of the organism we will work with. For us, the grant will primarily fund our experiments, which are extremely costly.
What helped you most in preparing the grant application? Do you have any advice for colleagues aiming to secure such prestigious funding?
Ironically, what helped me most—and simultaneously complicated the process—was being on a sort of improvised maternity leave with my daughter, who is now three years old. Stepping away from the daily lab routine, with its constant demands, gave me space to think. Walking with my daughter allowed me to reflect and work differently.
The existing team was also incredibly helpful. Having an idea is one thing, but executing it is another. Many methods we use are new, and part of the team conducted preliminary experiments and developed methodologies. We brainstormed and worked together to figure out the technical aspects.
Setting aside time specifically for writing was also crucial. Science is a relentless field with an endless "to-do list." I had to draw a clear line and dedicate one or two weeks solely to grant writing.
It’s inspiring that, as a mother of three children—two sons (15 and 10 years old) and a daughter (three years old)—you challenge the stereotype that women must choose between a top scientific career and a family. How do you balance family and work life?
It’s challenging. In the Czech Republic, there is a significant lack of childcare options for children under two years old. Faculty childcare facilities typically accept children only from 2.5 years onward.
When my husband and I couldn’t alternate caring for our daughter, I often had her with me in the lab. While it was wonderful to be with her, some moments were very tough. I hope universities set an example by offering better childcare options so researchers don’t have to interrupt their work entirely.
It seems that the Department of Cell Biology at the Faculty of Science is experiencing a "golden age," with its teams achieving significant success. What do you think is driving this?
The environment here is fantastic. A key factor is the efforts of Professor Jan Černý, who, during his tenure as department head, facilitated the establishment of four new research groups.
All of us in these groups returned from postdoctoral positions abroad and share that international experience, along with the challenge of starting new research teams. We support each other, share our frustrations, and celebrate successes together. This sense of companionship camaraderie greatly enhances the atmosphere.
This support was evident when you cheered for Jan Dobeš, head of the Laboratory of Microbial Immunology, as he received the "Invention" award at the Česká hlava awards.
Absolutely. Sharing both joy and difficulties when things don’t go as planned makes a big difference. The current leadership of our department – Professor Jan Brábek and Dr. Marian Novotný – also supports this collaborative approach, opening the door to two more new research groups. This strategy has clearly proven successful.
| Klára Hlouchová, PhD |
| Klára Hlouchová is a graduate of Biochemistry at the Faculty of Science, Charles University, where she also defended her dissertation. As a postdoctoral researcher, she worked at the University of Colorado Boulder in the USA under the supervision of Professor Shelley Copley, focusing on the evolution of proteins and metabolic pathways. She also collaborated on a project funded by the NASA Astrobiology Institute. Currently, she leads her own Synthetic Biology Laboratory at the Department of Cell Biology, Faculty of Science, Charles University. She is one of the few scientists in the Czech Republic to have repeatedly secured a grant from The Human Frontier Science Program. Her research has also been supported by the VW Stiftung foundation, the Czech Science Foundation, and Charles University, which awarded her the Primus grant, aimed at promising scientists to help them establish their own research teams and projects. |
