Current Opinion in Systems Biology最新文献

In cells, the microtubule network continually assembles and disassembles. The regulation of microtubule growth or shortening has almost exclusively been studied at their dynamic ends. However, microtubules are dynamic all along their entire shaft. A dynamic shaft increases the lifetime and length of a microtubule by reducing the shortening phases and promoting its regrowth. Here, we discuss how shaft dynamics can regulate microtubule network organization, intracellular transport, and polarization of the network.

Engineering new functions in the microbiome requires understanding how host genetic control and microbe–microbe interactions shape the microbiome. One key genetic mechanism underlying host control is the immune system. The immune system can promote stability in the composition of the microbiome by reshaping the ecological dynamics of its members, but the degree of stability will depend on the interplay between ecological context, immune system development, and higher-order microbe–microbe interactions. The eco-evolutionary interplay affecting composition and stability should inform the strategies used to engineer new functions in the microbiome. We conclude with recent methodological developments that provide an important path forward for both engineering new functionality in the microbiome and broadly understanding how ecological interactions shape evolutionary processes in complex biological systems.

Collective cell behaviors are essential for the shape and function of tissues. The last decades have provided unequivocal experimental evidence that tissue mechanics are key drivers of morphogenesis. In particular, the spatiotemporal coordination of cellular contractility, adhesion and volume regulation can drive morphogenetic events in various epithelia. At the same time, the epithelial sheets themselves have remarkable mechanical properties, being able to distribute mechanical stress throughout the whole material to resist the physical deformations necessary for their function. In this review, we address recent findings on epithelia morphogenesis and mechanical resistance and highlight the importance of quantitative new approaches for achieving novel understanding.

Enhancers are genomic elements that regulate gene expression through a variety of mechanisms. In neuronal systems, enhancer-promoter interactions regulate cell- and tissue-specific transcriptional programs, during neuronal specification and upon terminal differentiation, and play major roles in the tight regulation of activity-dependent mechanisms, such as in memory formation. Enhancers are also hotspots for non-coding genetic variants associated with neurological disorders, such as schizophrenia and Parkinson's disease (PD). Understanding how enhancer grammar informs gene expression programs in neuronal systems in development and disease remains a major challenge, and is a growing avenue to discover the molecular mechanisms directly altered by non-coding genetic variants. In this review, we discuss the diverse mechanisms by which enhancers integrate internal and external stimuli to regulate the gene expression programs that guide neuronal specification and sustain neuronal-specific and activity-dependent processes.

To reliably form and maintain structures with specific functions, many multicellular systems evolved to leverage the interplay between biochemical signaling, mechanics, and morphology.

We review mechanochemical feedback loops in cases where cell–cell contact-based Notch signaling drives fate decisions, and the corresponding differentiation process leads to contact remodeling. We compare different mechanisms for initial symmetry breaking and subsequent pattern refinement, as well as discuss how patterning outcomes depend on the relationship between biochemical and mechanical timescales.

We conclude with an overview of new approaches, including the study of synthetic circuits, and give an outlook on future experimental and theoretical developments toward dissecting and harnessing mechanochemical feedback.

The central nervous system develops from a pool of neural progenitors which, depending on their location and time of division, generate cells committed to differentiate into specific kinds of neurons or glia. In the last decades, the developmental neurobiology field has made important progress in understanding neural cell-type specification: key patterning mechanisms were discovered, the different waves of neurogenesis described, and the dynamics of cortical stratification elucidated. However, only recently, with the advent of single-cell genomics and organoid culturing methods, we were able to measure the transcriptional signatures of individual progenitors systematically and flexibly perturb human development. Together these fine-grained readouts and perturbation possibilities have allowed comparing neural differentiation between species and dissecting the relationship between progenitors' phenotype and fate commitment. This review summarizes recent in vivo and in vitro studies that have contributed to our understanding of temporal progression and coordination of neuronal cell specification across mammals.

Models of transcriptional regulation that assume equilibrium binding of transcription factors have been less successful at predicting gene expression from sequence in eukaryotes than in bacteria. This could be due to the non-equilibrium nature of eukaryotic regulation. Unfortunately, the space of possible non-equilibrium mechanisms is vast and predominantly uninteresting. The key question is therefore how this space can be navigated efficiently, to focus on mechanisms and models that are biologically relevant. In this review, we advocate for the normative role of theory—theory that prescribes rather than just describes—in providing such a focus. Theory should expand its remit beyond inferring mechanistic models from data, towards identifying non-equilibrium gene regulatory schemes that may have been evolutionarily selected, despite their energy consumption, because they are precise, reliable, fast, or otherwise outperform regulation at equilibrium. We illustrate our reasoning by toy examples for which we provide simulation code.

The physics of critical points lies behind the organization of various complex systems, from molecules to ecosystems. Several functional benefits emerge when operating at the edge of a critical point, at criticality, potentially explaining the optimality of biological function. Here, we propose that introducing the concept of criticality in developmental biology may explain remarkable features of embryonic development, such as collective behavior and fitness. Recent interdisciplinary studies approached embryonic processes with statistical physics frameworks and revealed that biochemical and biomechanical processes of embryonic development resemble critical phenomena. We discuss those processes, including gene expression, cell differentiation, and tissue mechanics, and challenge if criticality has a beneficial function during embryonic organization.