ERC FUNDED PROJECTS

The emergence of coherent behaviour is ubiquitous in the natural world and has long captivated biologists and physicists alike. One area of growing interest is the collective motion and synchronization arising within and between simple motile organisms. My goal is to develop and use a novel experimental approach to unravel the origins of spontaneous coherent motion in three model systems of biofluids: (1) the synchronization of the two flagella of green algae Chlamydomonas Rheinhardtii, (2) the metachronal wave in the cilia of protist Paramecium and (3) the collective motion of swimming microorganisms in active suspensions. Understanding the mechanisms leading to collective motion is of tremendous importance because it is crucial to many biological processes such as mechanical signal transduction, embryonic development and biofilm formation. Up till now, most of the work has been theoretical and has led to the dominant view that hydrodynamic interactions are the main driving force for synchronization and collective motion. Recent experiments have challenged this view and highlighted the importance of direct mechanical contact. New experimental studies are now crucially needed. The state-of-the-art of experimental approaches consists of observations of unperturbed cells. The key innovation in our approach is to dynamically interact with microorganisms in real-time, at the relevant time and length scales. I will investigate the origins of coherent motion by reproducing synthetically the mechanical signatures of physiological flows and direct mechanical interactions and track precisely the response of the organism to the perturbations. Our new approach will incorporate optical tweezers to interact with motile cells, and a unique μ-Tomographic PIV setup to track their 3D micron-scale motion. This proposal tackles a timely question in biophysics and will yield new insight into the fundamental principles underlying collective motion in active biological matter.

1 500 000 €

Start date: 2017-04-01, End date: 2022-03-31

Linear Parameter-Varying (LPV) systems are flexible mathematical models capable of representing Nonlinear (NL)/Time-Varying (TV) dynamical behaviors of complex physical systems (e.g., wafer scanners, car engines, chemical reactors), often encountered in engineering, via a linear structure. The LPV framework provides computationally efficient and robust approaches to synthesize digital controllers that can ensure desired operation of such systems - making it attractive to (i) high-tech mechatronic, (ii) automotive and (iii) chemical-process applications. Such a framework is important to meet with the increasing operational demands of systems in these industrial sectors and to realize future technological targets. However, recent studies have shown that, to fully exploit the potential of the LPV framework, a number of limiting factors of the underlying theory ask a for serious innovation, as currently it is not understood how to (1) automate exact and low-complexity LPV modeling of real-world applications and how to refine uncertain aspects of these models efficiently by the help of measured data, (2) incorporate control objectives directly into modeling and to develop model reduction approaches for control, and (3) how to see modeling & control synthesis as a unified, closed-loop system synthesis approach directly oriented for the underlying NL/TV system. Furthermore, due to the increasingly cyber-physical nature of applications, (4) control synthesis is needed in a plug & play fashion, where if sub-systems are modified or exchanged, then the control design and the model of the whole system are only incrementally updated. This project aims to surmount Challenges (1)-(4) by establishing an innovative revolution of the LPV framework supported by a software suite and extensive empirical studies on real-world industrial applications; with a potential to ensure a leading role of technological innovation of the EU in the high-impact industrial sectors (i)-(iii).

1 493 561 €

Start date: 2017-09-01, End date: 2022-08-31

Natural selection is supposed to keep lethal alleles (dysfunctional or deleted copies of crucial genes) in check. Yet, in a balanced lethal system the frequency of lethal alleles is inflated. Because two forms of a chromosome carry distinct lethal alleles that are reciprocally compensated for by functional genes on the alternate chromosome form, both chromosome forms – and in effect their linked lethal alleles – are required for survival. The inability of natural selection to purge balanced lethal systems appears to defy evolutionary theory. How do balanced lethal systems originate and persist in nature? I suspect the answer to this pressing but neglected research question can be found in the context of supergenes in a balanced polymorphism – a current, hot topic in evolutionary biology. Chromosome rearrangements can lock distinct beneficial sets of alleles (i.e. supergenes) on two chromosome forms by suppressing recombination. Now, balancing selection would favour possession of both supergenes. However, as a consequence of suppressed recombination, unique lethal alleles could become fixed on each supergene, with natural selection powerless to prevent collapse of the arrangement into a balanced lethal system. I aim to explain the evolution of balanced lethal systems in nature. As empirical example I will use chromosome 1 syndrome, a balanced lethal system observed in newts of the genus Triturus. My research team will: Reconstruct the genomic architecture of this balanced lethal system at its point of origin [PI project]; Conduct comparative genomics with related, unaffected species [PhD project]; Determine gene order of the two supergenes involved [Postdoc project I]; and Model the conditions under which this balanced lethal system could theoretically have evolved [Postdoc project II]. Solving the paradox of chromosome 1 syndrome will allow us to understand balanced lethal systems in general and address the challenges they pose to evolutionary theory.

1 499 869 €

Start date: 2019-02-01, End date: 2024-07-31

Sexual reproduction depends on the programmed induction of DNA double-strand breaks (DSBs) and their ensuing repair by homologous recombination. This complex process is essential for sexual reproduction because it ultimately allows the pairing and separation of homologous chromosomes during formation of haploid gametes. Although meiotic recombination has been investigated for decades, many of the underlying molecular processes remain unclear, largely due to the lack of biochemical studies. I have recently made important progress by, for the first time, successfully purifying proteins involved in two aspects of meiotic recombination: DSB formation and the final stage of formation of the crossovers that are a central raison-d’être of meiotic recombination. This has opened new avenues for future research that I intend to pursue in my own laboratory. Here, I propose a set of biochemical approaches, complemented by molecular genetics methods, to gain insights into four central problems: (i) How meiotic proteins collaborate to induce DSBs; (ii) How DSB proteins interact with components that form the axes of meiotic chromosomes; (iii) How proteins involved at later stages of recombination form crossovers; and (iv) How crossover proteins interact with components of synapsed chromosomes. For each problem, I will set up in vitro systems to probe the activities of the players involved, their interactions with DNA, and their assembly into macromolecular complexes. In addition, I propose to develop new methodology for identifying proteins that are associated with DNA that has undergone recombination-related DNA synthesis. My goal is to gain insights into the mechanisms that govern meiotic recombination. Importantly, these mechanisms are intimately linked not only to gamete formation, but also to the general recombination pathways that all cells use to maintain genome stability. In both contexts, our findings will be relevant to the development and avoidance of disease states.

1 499 075 €

Start date: 2019-07-01, End date: 2024-06-30