Kamila B. Muchowska, PhD

Research as Chargée de recherche - from October 2019 (Institut de Science et d'Ingénierie Supramoléculaires, Strasbourg):

1) I am applying my engineering and physical chemistry background to build setups that mimic the out-of-equilibrium conditions required to initiate non-enzymatic precursors of ancient metabolic pathways. The goal is to obtain a dynamic system with potentially life-like emergent properties and push the boundaries of non-enzymatic proto-biochemistry towards a more life-like regime, under a high environmental parsimony.

2) Many cofactors have a simple chemical structure and contain either a small heterocycle or a transition metal set within a small-peptide scaffold. Little is known about their prebiotic synthesis in a context that recapitulates biosynthesis, and even less is known about the functional rationale behind their structure. For this reason, I set out to study the chemical evolution of cofactors and the prebiotic history of biocatalysis.

Research as PDRA - January 2016 to September 2019 (Moran Lab, Institut de Science et d'Ingénierie Supramoléculaires, Strasbourg):

Metabolism is considered a critical feature of living systems. Its emergence from (geo)chemistry and self-organisation into biochemistry may arguably landmark a transition from non-life to life some 4 billion years ago.

In phase one of my postdoctoral work (2016-2018), we showed that reactions of known biochemical carbon fixation pathways, for instance the rTCA (reductive Krebs) cycle and the reductive AcCoA pathway, might have been able to operate without enzymes on the early Earth, and therefore may have originated as prebiotic chemistry. These reactions rely heavily on iron - the second most abundant metal on our planet (after aluminium).

Highlights:

rTCA: F1000Prime, CNRS, TechnoScience, CNRS 2017 top papers VIVANT (Life)
AcCoA: F1000Prime, phys.org, Spektrum.de, Investigación y Ciencia, TechnoScience, CNRS, Unistra

Subsequently (2018-2019), in a quest towards self-organising systems, we found that iron salts in warm water can trigger the formation of a complex reaction network from pyruvate and glyoxylate. The network spans most of the biological Krebs (TCA) and glyoxylate cycle reactions and intermediates, including five universal metabolic precursors. Next, we expanded the system towards amino acids, and my lab colleagues - towards thioesters. The high parsimony of the Krebs cycle and the iron-powered complex network could mean that a system like ours was a non-enzymatic prebiotic precursor to known biochemical pathways. These findings can be considered a major advance in understanding the origins of life’s most central biochemistry.

Highlights: F1000Prime, C&EN, phys.org, Earth Pages, Science Bulletin, Futura, Techno Science, CNRS, Unistra, American Society for Microbiology (video), La Brújula de la ciencia (podcast)

PhD research - September 2016 to September 2015 (Cockroft Lab, University of Edinburgh):

Non-covalent interactions involve different types of generally weak, attractive or repulsive forces arising between molecules or parts of the same molecule. Their role is vital in governing the shape and function of biologically significant molecules (e.g. DNA, proteins and enzymes), properties of materials and the activity of drug molecules. Since most of chemical and biological processes take place in solution, it is particularly important to know how interactions with solvent molecules affect interactions between – and within – the dissolved systems. However, predicting and quantifying solvent effects on non-covalent interactions is often very challenging. The research I carried out encompassed modifications of electrostatic properties of simple molecules by the solvent, probing the differences in strength of various interactions upon isotopic substitution and investigating the physical nature of weak interactions ever-present in peptides/proteins. I studied these phenomena using a small-molecule foldamer able to adopt two distinct geometrical states, depending on the interactions it undergoes, which allowed for quantitative measurements in a wide range of solvents.