245 results match your criteria: "Center for Cell Analysis and Modeling[Affiliation]"

The reaction-diffusion (RD) system is widely assumed to account for many complex, self-organized pigmentation patterns in natural organisms. However, the specific configurations of such RD networks and how RD systems interact with positional information (i.e.

View Article and Find Full Text PDF

Monocytes are critical in controlling tissue infections and inflammation. Monocyte dysfunction contributes to the inflammatory pathogenesis of cystic fibrosis (CF) caused by CF transmembrane conductance regulator (CFTR) mutations, making CF a clinically relevant disease model for studying the contribution of monocytes to inflammation. Although CF monocytes exhibited adhesion defects, the precise mechanism is unclear.

View Article and Find Full Text PDF

Gene expression is orchestrated by transcription factors, which function within the context of a three-dimensional genome. Zinc-finger protein 143 (ZNF143/ZFP143) is a transcription factor that has been implicated in both gene activation and chromatin looping. To study the direct consequences of ZNF143/ZFP143 loss, we generated a ZNF143/ZFP143 depletion system in mouse embryonic stem cells.

View Article and Find Full Text PDF

Microtubule acetylation is implicated in regulating cell motility, yet its physiological role in directional migration and the underlying molecular mechanisms have remained unclear. This knowledge gap has persisted primarily due to a lack of tools capable of rapidly manipulating microtubule acetylation in actively migrating cells. To overcome this limitation and elucidate the causal relationship between microtubule acetylation and cell migration, we developed a novel optogenetic actuator, optoTAT, which enables precise and rapid induction of microtubule acetylation within minutes in live cells.

View Article and Find Full Text PDF

Biochemical interactions at membranes are the starting points for cell signaling networks. But bimolecular reaction kinetics are difficult to experimentally measure on 2-dimensional membranes and are usually measured in volumetric assays. Membrane tethering produces confinement and steric effects that will significantly impact binding rates in ways that are not readily estimated from volumetric measurements.

View Article and Find Full Text PDF

Transcription factors bind to sequence motifs and act as activators or repressors. Transcription factors interface with a constellation of accessory cofactors to regulate distinct mechanistic steps to regulate transcription. We rapidly degraded the essential and pervasively expressed transcription factor ZNF143 to determine its function in the transcription cycle.

View Article and Find Full Text PDF

Immune digital twins for complex human pathologies: applications, limitations, and challenges.

NPJ Syst Biol Appl

November 2024

Biocomplexity Institute and Department of Intelligent Systems Engineering, Indiana University, Bloomington, Indiana, 47408, USA.

Digital twins represent a key technology for precision health. Medical digital twins consist of computational models that represent the health state of individual patients over time, enabling optimal therapeutics and forecasting patient prognosis. Many health conditions involve the immune system, so it is crucial to include its key features when designing medical digital twins.

View Article and Find Full Text PDF

Classifying the molecular functions of transcription factors beyond activation and repression.

Genes Dev

November 2024

Center for Cell Analysis and Modeling, University of Connecticut, Farmington, Connecticut 06030, USA

Notch signaling is a highly conserved pathway activated by dynamic cellular interactions that initiates a molecular cascade that ultimately drives changes in gene expression. The Notch transcriptional complex (NTC) regulates genes that influence development and homeostasis. In this issue of , Rogers and colleagues (doi:10.

View Article and Find Full Text PDF

NeuroSCAN: Exploring Neurodevelopment via Spatiotemporal Collation of Anatomical Networks.

bioRxiv

October 2024

Department of Neuroscience and Department of Cell Biology, Wu Tsai Institute, Yale University, New Haven, CT, USA.

Volume electron microscopy (vEM) datasets such as those generated for connectome studies allow nanoscale quantifications and comparisons of the cell biological features underpinning circuit architectures. Quantifications of cell biological relationships in the connectome result in rich multidimensional datasets that benefit from data science approaches, including dimensionality reduction and integrated graphical representations of neuronal relationships. We developed NeuroSCAN, an online open-source platform that bridges sophisticated graph analytics from data science approaches with the underlying cell biological features in the connectome.

View Article and Find Full Text PDF

Astrocytes initiate autophagic flux and maintain cell viability after internalizing non-active native extracellular α-synuclein.

Mol Cell Neurosci

December 2024

Biology Department, University of Hartford, 200 Bloomfield Avenue, West Hartford, CT 06117, United States of America. Electronic address:

Astrocytes are tasked with regulating the synaptic environment. Early stages of various neurodegenerative diseases are characterized by synapse loss, and astrocytic atrophy and dysfunction has been proposed as a possible cause. α-Synuclein (αS) is a highly expressed neuronal protein located in the synapse that can be released in the extracellular space.

View Article and Find Full Text PDF

Hypoxia is one of the key factors in the tumor microenvironment regulating nearly all steps in the metastatic cascade in many cancers, including in breast cancer. The hypoxic regions can however be dynamic with the availability of oxygen fluctuating or oscillating. The canonical response to hypoxia is relayed by transcription factor Hypoxia-Inducible Factor 1 (HIF-1), which is stabilized in hypoxia and acts as the master regulator of a large number of downstream genes.

View Article and Find Full Text PDF

Foundations of a Compositional Systems Biology.

ArXiv

November 2024

Center for Cell Analysis and Modeling, Department of Molecular Biology and Biophysics, University of Connecticut Health, Farmington, Connecticut, USA.

Composition is a powerful principle for systems biology, focused on the interfaces, interconnections, and orchestration of distributed processes to enable integrative multiscale simulations. Whereas traditional models focus on the structure or dynamics of specific subsystems in controlled conditions, compositional systems biology aims to connect these models, asking critical questions about : What variables should a submodel expose through its interface? How do coupled models connect and translate across scales? How do domain-specific models connect across biological and physical disciplines to drive the synthesis of new knowledge? This approach requires robust software to integrate diverse datasets and submodels, providing researchers with tools to flexibly recombine, iteratively refine, and collaboratively expand their models. This article offers a comprehensive framework to support this vision, including: a conceptual and graphical framework to define interfaces and composition patterns; standardized schemas that facilitate modular data and model assembly; biological templates that integrate detailed submodels that connect molecular processes to the emergence of the cellular interface; and user-friendly software interfaces that empower research communities to construct and improve multiscale models of cellular systems.

View Article and Find Full Text PDF

Cellular condensates often consist of 10s to 100s of distinct interacting molecular species. Because of the complexity of these interactions, predicting the point at which they will undergo phase separation is daunting. Using experiments and computation, we therefore studied a simple model system consisting of polySH3 and polyPRM designed for pentavalent heterotypic binding.

View Article and Find Full Text PDF

bnglViz: online visualization of rule-based models.

Bioinformatics

June 2024

R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut School of Medicine, Farmington, CT 06030, United States.

Motivation: Rule-based modeling is a powerful method to describe and simulate interactions among multi-site molecules and multi-molecular species, accounting for the internal connectivity of molecules in chemical species. This modeling technique is implemented in BioNetGen software that is used by various tools and software frameworks, such as BioNetGen stand-alone software, NFSim simulation engine, Virtual Cell simulation and modeling framework, SmolDyn and PySB software tools. These tools exchange models using BioNetGen scripting language (BNGL).

View Article and Find Full Text PDF

Transcription factors bind to sequence motifs and act as activators or repressors. Transcription factors interface with a constellation of accessory cofactors to regulate distinct mechanistic steps to regulate transcription. We rapidly degraded the essential and ubiquitously expressed transcription factor ZNF143 to determine its function in the transcription cycle.

View Article and Find Full Text PDF

Within a given tissue, the stem cell niche provides the microenvironment for stem cells suitable for their self-renewal. Conceptually, the niche space constrains the size of a stem-cell pool, as the cells sharing the niche compete for its space. It has been suggested that either neutral- or non-neutral-competition of stem cells changes the clone dynamics of stem cells.

View Article and Find Full Text PDF

Cancer progression is a complex process involving interactions that unfold across molecular, cellular, and tissue scales. These multiscale interactions have been difficult to measure and to simulate. Here, we integrated CODEX multiplexed tissue imaging with multiscale modeling software to model key action points that influence the outcome of T cell therapies with cancer.

View Article and Find Full Text PDF

As local regions in the tumor outstrip their oxygen supply, hypoxia can develop, affecting not only the cancer cells, but also other cells in the microenvironment, including cancer associated fibroblasts (CAFs). Hypoxia is also not necessarily stable over time, and can fluctuate or oscillate. Hypoxia Inducible Factor-1 is the master regulator of cellular response to hypoxia, and can also exhibit oscillations in its activity.

View Article and Find Full Text PDF

Tumor hypoxia is a common microenvironmental factor in breast cancers, resulting in stabilization of Hypoxia-Inducible Factor 1 (HIF-1), the master regulator of hypoxic response in cells. Metabolic adaptation by HIF-1 results in inhibition of citric acid cycle, causing accumulation of lactate in large concentrations in hypoxic cancers. Lactate can therefore serve as a secondary microenvironmental factor influencing cellular response to hypoxia.

View Article and Find Full Text PDF

Common genetic variants in the repressive GATA-family transcription factor (TF) TRPS1 locus are associated with breast cancer risk, and luminal breast cancer cell lines are particularly sensitive to TRPS1 knockout. We introduced an inducible degron tag into the native TRPS1 locus within a luminal breast cancer cell line to identify the direct targets of TRPS1 and determine how TRPS1 mechanistically regulates gene expression. We acutely deplete over 80 percent of TRPS1 from chromatin within 30 minutes of inducing degradation.

View Article and Find Full Text PDF

Hypoxia-inducible factor-1 (HIF-1) is the master regulator of cellular response to hypoxia, and is activated in many cancers contributing to many steps in the metastatic cascade by acting as a key transcription co-regulator for a large number of downstream genes. Presence of hypoxia within a tumor is spatially nonuniform, and can also by dynamic. Further, although HIF-1 is primarily stabilized and activated by lack of molecular O, its stability is also affected by other factors present in the tumor microenvironment.

View Article and Find Full Text PDF

T-tubules (TT) form a complex network of sarcolemmal membrane invaginations, essential for well-co-ordinated excitation-contraction coupling (ECC) and thus homogeneous mechanical activation of cardiomyocytes. ECC is initiated by rapid depolarization of the sarcolemmal membrane. Whether TT membrane depolarization is active (local generation of action potentials; AP) or passive (following depolarization of the outer cell surface sarcolemma; SS) has not been experimentally validated in cardiomyocytes.

View Article and Find Full Text PDF

Cellular condensates often consist of 10s to 100s of distinct interacting molecular species. Because of the complexity of these interactions, predicting the point at which they will undergo phase separation into discrete compartments is daunting. Using experiments and computation, we therefore studied a simple model system consisting of 2 proteins, polySH3 and polyPRM, designed for pentavalent heterotypic binding.

View Article and Find Full Text PDF

Drosophila male germline stem cells (GSCs) reside at the tip of the testis and surround a cluster of niche cells. Decapentaplegic (Dpp) is one of the well-established ligands and has a major role in maintaining stem cells located in close proximity. However, the existence and the role of the diffusible fraction of Dpp outside of the niche have been unclear.

View Article and Find Full Text PDF