Macromolecular protein complexes perform essential biological functions across life forms. The assembly of such complexes is known to be regulated at the level of gene transcription, but little is known about the factors that control their assembly once the mature protein subunits enter their target space (cytoplasm, membrane, or cell wall)…
Organisms are an evolutionary masterpiece of feedback control, featuring a mind-boggling capacity to self-correct. In this talk, we discuss our attempts to both understand feedback control in cells and to forward engineer it with de novo designed proteins.
Visual systems detect many features of natural scenes, including motion. Motion detection guides critical behaviors like hunting, evading predators, and finding mates. It can be framed as an inference problem, in which light intensity measurements are combined to estimate a latent variable of image velocity. Interestingly, several patterns of…
Nucleosomes help structure chromosomes by compacting DNA into fibers. Chromatin organization plays an important role for regulating gene expression; however, due to the highly crowded nuclear environment and the nanometer length scales of chromatin fibers, it has been very difficult to visualize chromatin in vivo. We have overcome this…
Microtubules are active biological polymers known to stochastically switch between phases of growth and shrinkage, a behavior termed ‘dynamic instability’. Microtubule treadmilling, in which the microtubule plus end grows while the minus end shrinks, is also observed in cells. While dynamic instability has been widely studied
I will describe a new approach that we are currently developing to describe developmental dynamics. We are using simple machine learning techniques to project the dynamics of the Drosophila gap genes onto a low dimensional space, allowing us to build "geometric" models. We uncover a relatively simple dynamics in latent space, where we…
DNA Folding in Sperm
In sperm, DNA is tightly compacted to create a small, hydrodynamic sperm head. This dramatic reorganization of the nucleus is carried out by protamine proteins that fold the DNA into loops and toroids. Here, I'll talk about the pathway and physical mechanism of that DNA folding. We will look at…
Response in immune repertories
The immune repertoire responds to a wide variety of pathogenic threats. Immune repertoire sequencing experiments give us insight into the composition of these repertoires. Since the functioning of the repertoire relies on statistical properties, statistical analysis is needed to identify responding…
Mechanics, geometry and topology of cell nuclei and metaphase chromosomes
I will discuss studies of the mechanics and structure of metaphase chromosomes and nuclei extracted from mammalian cells using glass micropipettes. Using a combination of mechanical, biochemical and genetic approaches we have shown that the…
Physics of collective cell sensing
The physical limits to chemical sensing have been established and tested for single cells. However, recent experiments have demonstrated that cells can surpass these limits when they communicate. The theoretical limits to the precision of collective sensing are still poorly…
Modeling the minimal cell: Integration of experiments, theory, and simulations
JCVI-syn3A, a robust minimal cell with a 543 kbp genome and 493 genes, provides a versatile
platform to study the principles of life (Breuer et al. eLife 2019). Using the vast amount of
experimental information available on its…
Collective migration of cohesive groups of cells is a hallmark of the tissue remodeling events that underlie embryonic morphogenesis, wound repair and cancer invasion. In this collective migration, supra-cellular properties such as collective polarization or force generation emerge and eventually control large- scale…
In physics and engineering dimensionless numbers frequently help to characterize the state of a system. I will present a series of vignettes about unusually large dimensionless numbers that arise in brain science. These can indicate issues that are poorly understood, and in some cases clearly misunderstood.
Early embryogenesis of most metazoans is characterized by rapid and synchronous cleavage divisions. After fertilization, Drosophila embryos undergo 13 swift rounds of DNA replication and mitosis without cytokinesis, resulting in a multinucleated syncytium containing about 6,000 nuclei. The very first cycles involve substantial flows, both in…
Optical reporters of neural activity have improved dramatically over the past decade. Recent developments in optical imaging approaches have unlocked the power of these indicators and can now provide real-time read-outs from large populations of brain cells in a wide range of living organisms. We have recently…
The human adaptive immune system makes robust decisions which regulate quantitative and qualitative parameters of a complex physiological system, to prevent invasion and destruction of tissues by the enormous array of microorganisms which share our environment. Remarkably, these decisions are made by a…
In vivo, the human genome folds into a characteristic ensemble of 3D structures. The mechanism driving the folding process remains unknown. A theoretical model for chromatin (minimal chromatin model) that explains the folding of interphase chromosomes and generates chromosome conformations consistent with experimental data will be presented…
Toward circuits optogenetics
Since the discovery of Channelrhodopsin and the first demonstration of photo-evoked action potentials in mammalian cells, optogenetics is progressively revolutionizing neuroscience research, opening perspectives both in fundamental and in medical research still unimaginable until few years…
Pattern formation and self-organization in biological flows
Complex life above a certain size would not be possible without a circulatory system. Both plants and animals have developed vascular systems of striking complexity to solve the problem of nutrient delivery, waste removal, and…
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