Research Projects

Carbohydrates (sugars) are ubiquitous in the living cell and fulfill essential roles. Our immune system recognizes carbohydrates as self or foreign, and viruses recognize human cell-surface glycolipids as entrance points for infection.  Also in medicine, carbohydrates play important roles as anti-infectives, and in vaccines for instance.

Recent attempts to mimic enzyme catalysis using simple, prebiotically relevant peptides have been successful in enhancing various reactions. However, the on-demand, temporal or spatial regulation of such processes by external triggers remains a great challenge. Light irradiation is an ideal trigger for regulating molecular functionality, since it can be precisely manipulated in time and space, and because most reaction mediums do not react to light.

In the origin of life, the transition from small building blocks to complex, organised assemblies set the stage for the emergence of biological systems. These supramolecular structures bridge the gap between simple organic molecules and the complex, organised systems that characterise living systems.

Liquid-liquid phase separation (LLPS) or coacervation is a key process to regulate self-assembly of proteins and other molecules within living cells. LLPS occurs within macromolecular solutions generating a liquid concentrated phase that is separated out of solution somewhat similar to the way oil de-mixes from water.

Archaea are established as a separate branch in the tree of life next to bacteria. Eukaryotes are no longer considered a distinct and separate branch, but instead they are considered to be recent members of the archaeal branch. While the effect of controlled and synthetic 3D culture environments on a range of eurkaryotic cell types are widely recognized and can be harnessed to learn about and steer specific cell behaviours, application of this concept in archaea is practically non-existent.

Multicellularity represents one of the most significant evolutionary transitions in the history of life, and a key topic in Origin of Life research. Understanding its underlying mechanisms offers insight into how complexity arises.

This project addresses the question of how life may emerge from inanimate chemical systems. It focuses on self-replicating molecules (i.e. molecules that are capable of promoting their own formation). A limited number of such molecules have been reported (for an example of the systems on which this project is based, see: Science 2010, 327, 1502).

Current theory holds that, during the early stages of chemical evolution, microscopic compartments called protocells played a critical role, because they were able to sequester and concentrate small molecules that would react together, to eventually yield the building blocks of life. 

The complex problem of the origin of life can be approached from different angles and scientific disciplines: while chemists may attempt to extrapolate from their understanding of self-organization processes in organochemical networks towards the first living systems, biologists may reason ‘from hindsight’, based on their knowledge of extant life and their reconstruction of the most plausible pathways that led to its emergence.

A main feature in the origin of complex life is the translation system by means of the near-universal genetic code: stored information contained in large molecules (DNA) is copied onto smaller molecules (RNA) that are “read” by ribosomes, which make proteins based on the information.

Whether exoplanets may host life as we know it is often assessed in terms of the circumstellar  ‘habitable zone’, where liquid water could exist on the planetary surface. However, this concept is only well-defined for planets with an Earth-like atmospheric composition. Similarly, several proposed biosignatures for exoplanets (i.e., signs of the presence of life as we know it), such as dimethyl sulfide and phosphine, are molecules which on Earth are only produced by living organisms, but for which abiotic formation routes may operate on other planets.

Most enzymes rely on a cofactor for their functioning. These accessory molecules or ions are essential for enabling protein-based catalysis of reactions that are crucial to life. Cofactor-dependent enzymes have evolved to efficiently capture, bind, and utilize specific cofactors for catalysis.

Single-molecule fluorescence studies can provide valuable information about the structural dynamics, and therefore the function, of integral membrane transport proteins. This project aims to compare the functional dynamics of archaeal and human secondary active transporters using confocal and total internal fluorescence (TIRF) microscopy, to compare to optical tweezers data [1].

Building on our recent work enabling the single-molecule measurement of transmembrane transport proteins in lipid nanodiscs using optical tweezers [1], this project aims to expand our understanding of how the physical and chemical properties of the environment impact the stability and function of archaeal and human secondary active transporters.

ESCRT-III proteins form supramolecular structures that are essential for membrane remodelling processes across the tree of life. In archaea and eukaryotes, the ESCRT-III proteins assemble into polymers that cut membrane tubes together with Vps4, an AAA–ATPase.

Oceanic islands harbor a disproportional fraction of Earth’s biodiversity, but are also host to many species that are threatened with extinction. Advantages of isolation are reduced competition, predation and parasitism, availability of new ecological niches, and opportunity for unique traits (that might become very advantageous in the future) to become fixed due to genetic drift. That is, an isolated system is a cradle for new forms of life.

Exoplanet search programs have found by now rocky exoplanets around solar-type stars, but also a large population of them around low mass stars; these are the most abundant stars in our galaxy and thus of prime interest also for finding extraterrestrial life.

One of the key features of life is the presence of its essential molecules such as amino acids, proteins, sugars and DNA as one mirror image form. These single handed chiral (from Greek χειρ (kheir), “hand”) structures are considered crucial for the evolution of life on the earth; a phenomenon called homochirality.

The cytoplasm of cells is a highly crowded environment and it is intriguing to see how biomolecular processes still can work in such an environment. Given that cells constantly convert energy, the cytoplasm has also been described as ‘active matter’.

Compartmentalization plays a crucial role in early life, facilitating the emergence of complex life forms from simple prebiotic reaction networks. In prokaryotic cells and primitive protocells, spatial division by membranes is not present. Instead, compartmentalization is enabled through the process of phase separation of RNA-protein systems, forming distinct liquid-like droplets, also known as biological condensates.