A5018785790- Gene Regulatory Network Analysis
- Microbial Metabolic Engineering and Bioproduction
- Cellular Mechanics and Interactions
- Bioinformatics and Genomic Networks
- Cancer Cells and Metastasis
- Pluripotent Stem Cells Research
- Formal Methods in Verification
- Hippo pathway signaling and YAP/TAZ
- 3D Printing in Biomedical Research
- Genetics, Bioinformatics, and Biomedical Research
- Skin and Cellular Biology Research
- Nerve injury and regeneration
- 3D Shape Modeling and Analysis
- Microtubule and mitosis dynamics
- Analog and Mixed-Signal Circuit Design
- Cell Image Analysis Techniques
- Heat shock proteins research
- Neurogenesis and neuroplasticity mechanisms
- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- Scientific Computing and Data Management
- Model-Driven Software Engineering Techniques
- Advanced Data Storage Technologies
- Wnt/β-catenin signaling in development and cancer
- Genetic factors in colorectal cancer
Jacobs (United Kingdom)
2024
Microsoft Research (United Kingdom)
2012-2023
Macquarie University
2019
Medical Research Council
2017-2018
Wellcome/MRC Cambridge Stem Cell Institute
2017-2018
Stem Cell Institute
2017-2018
Wellcome Trust
2017-2018
University of Cambridge
2017
King's College London
2017
Guy's Hospital
2017
Chaste — Cancer, Heart And Soft Tissue Environment is an open source C++ library for the computational simulation of mathematical models developed physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology cancer development. A large number studies have enabled performed, including high-performance investigations defibrillation on realistic human geometries. New initiation growth tumours developed. In particular, cell-based simulations...
The gene regulatory circuitry through which pluripotent embryonic stem (ES) cells choose between self-renewal and differentiation appears vast has yet to be distilled into an executive molecular program. We developed a data-constrained, computational approach reduce complexity derive set of functionally validated components interaction combinations sufficient explain observed ES cell behavior. This minimal set, the simplest version comprises only 16 interactions, 12 components, three inputs,...
Epidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation. The transition the two states, termed commitment, is poorly understood. Here, we characterise commitment by integrating transcriptomic proteomic data from disaggregated primary human keratinocytes held in suspension to induce Cell detachment induces several protein phosphatases, five of which - DUSP6, PPTC7, PTPN1, PTPN13 PPP3CA – promote differentiation negatively regulating ERK MAPK...
Cell migration in the intestinal crypt is essential for regular renewal of epithelium, and continued upward movement cells a key characteristic healthy dynamics. However, driving force behind this unknown. Possibilities include mitotic pressure, active driven by motility cues, or negative pressure arising from cell loss at collar. It possible that combination factors together coordinate migration. Here, three different computational models are used to provide insight into mechanisms underpin...
Predictive biology is elusive because rigorous, data-constrained, mechanistic models of complex biological systems are difficult to derive and validate. Current approaches tend construct examine static interaction network models, which descriptively rich but often lack explanatory predictive power, or dynamic that can be simulated reproduce known behavior. However, in such implicit assumptions introduced as typically only one mechanism considered, exhaustively investigating all scenarios...
The role of the basement membrane is vital in maintaining integrity and structure an epithelial layer, acting as both a mechanical support forming physical interface between cells surrounding connective tissue. function this explored here context monolayer that lines colonic crypt, test-tube shaped invaginations punctuate lining intestine coordinate regular turnover to replenish layer every few days. To investigate consequence genetic mutations perturb system dynamics can lead colorectal...
A number of quantum technologies require macroscopic mechanical oscillators possessing ultra-high motional Q-factors. These can be used to explore the limits mechanics, develop sensors and test nature gravity. One approach is trap nanometer micron-sized particles in 3D; however, use ion or optical traps suffers from a difficulties including electrodynamic noise due patch fields, damage unwanted laser heating, difficulty reaching low pressures particle loss. In this work, we report completely...
Curative intervention is possible if colorectal cancer identified early, underscoring the need to detect earliest stages of malignant transformation. A candidate biomarker expanded proliferative zone observed in crypts before adenoma formation, also found irradiated crypts. However, underlying driving mechanism for this not known. Wnt signaling a key regulator proliferation, and elevated implicated cancer. Nonetheless, how cells differentiate signals varying strengths understood. We use...
Studying the gene regulatory networks (GRNs) that govern how cells change into specific cell types with unique roles throughout development is an active area of experimental research. The fate specification process can be viewed as a biological program prescribing system dynamics, governed by network genetic interactions. To investigate possibility GRNs are not fixed but rather their topology, for example progress through commitment, we introduce concept Switching Gene Regulatory Networks...
Abstract During differentiation and reprogramming new cell identities are generated by reconfiguration of gene regulatory networks. Here we combined automated formal reasoning with experimentation to expose the logic network activation during induction naïve pluripotency. We find that a Boolean architecture defined for maintenance state embryonic stem cells (ESC) also explains transcription factor behaviour potency resetting from primed Computationally identified trajectories were...
We present a framework called the Reasoning Engine, which implements Satisfiability Modulo Theories (SMT)-based methods within unified computational environment to address diverse biological analysis problems. The Engine was used reproduce results from key scientific studies, as well supporting new research in stem cell biology. utilizes an intermediate language for encoding partially specified discrete dynamical systems, bridges gap between high-level domain-specific languages and low-level...
Abstract Epidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation. The transition the two states, termed commitment, is poorly understood. Here we characterise commitment by integrating transcriptomic proteomic data from disaggregated primary human keratinocytes held in suspension for up to 12h induce We find that detachment induces network of protein phosphatases. pro-commitment phosphatases – including DUSP6, PPTC7, PTPN1, PTPN13 PPP3CA promote...
Abstract A recurring set of small sub-networks have been identified as the building blocks biological networks across diverse organisms. These network motifs associated with certain dynamical behaviors and define key modules that are important for understanding complex programs. Besides studying properties in isolation, existing algorithms often evaluate occurrence frequency a specific motif given compared to random similar structure. However, it remains challenging relate structure observed...