Biology subjects

Shaw, E.

Publications and source records attributed to Shaw, E..

4 recordsLinked to original sources

bioRxiv2025

Precision targeting of autoreactive B cells in systemic lupus erythematosus using anti-9G4 idiotope synthetic immune receptor T cells

Chimeric antigen receptor (CAR)-T cell therapies can induce drug-free remission in systemic lupus erythematosus (SLE), but indiscriminate B cell targeting causes immunosuppression, unnecessary infections, and cytokine toxicities that preclude widespread use. Here, we overcome this by targeting the 9G4 idiotope, a shared structural feature of pathogenic B cell receptors encoded by the IGHV4-34 gene. We engineered anti-9G4 CAR-T cells and chimeric TCR-T cells to selectively eliminate autoreactive B cells while preserving protective immunity. Both platforms eradicated autoreactive B cells and autoantibodies in vitro and in vivo, spared normal B cells, and markedly reduced cytokine release compared to conventional CAR-T cells. This precision extended to cold agglutinin disease and lymphoma. These findings establish a framework for IGHV idiotope-directed cellular therapies for treating autoimmune and neoplastic diseases while preserving immune competence.

immunology↗

bioRxiv2025

A Systems-Level ODE Model of B-Oxidation: Algorithmic Flux Optimization and Simulation of MCADD Pathophysiology

We introduce a computational model that simulates {beta}-oxidation under varying metabolic conditions by solving a system of ordinary differential equations (ODEs) that describe the flux of key intermediates and cofactors. The model captures the stepwise breakdown of saturated, even-chain fatty acids, incorporating dynamic cofactor coupling and product drainage via infinite sinks to maintain numerical stability and biological realism. An optimization routine based on Nelder-Mead simplex refines initial conditions to minimize system residuals. When simulating medium-chain acyl-CoA dehydrogenase deficiency (MCADD), the model predicts metabolite accumulation upstream of the enzymatic block and downstream depletion - highlighting the sensitivity of flux distributions to enzymatic constraints. This work frames kinetic modeling as a tractable method to interrogate systems-level metabolic imbalance and offers a modular framework for future expansions.

systems biology↗

bioRxiv2025

Layers to Leaves: A Suite of Modular 3D Printed Hydroponics Components for Research and Education

Hydroponics is a widely utilized technique to precisely control the plant growing environment and maximize productivity. In some cases, hydroponics systems can be expensive and require specialized expertise to build and maintain. Here, we present a suite of 3D-printed devices that can be constructed into a single or double tower hydroponics system. This system is easily scalable to fit the needs of a user and can be implemented in a variety of research and educational contexts. Components in this suite can be made from inexpensive plastic filament using household-grade 3D printers. The vertical design of these systems allows for users to maximize space-use-efficiency in growth chambers, greenhouses, or even classrooms. We describe the construction of our system and provide example data from a validation study growing spinach (Spinacia oleracea L.) under different salinity conditions. This suite of 3D printed components can be utilized by researchers and educators alike to capitalize on the benefits of hydroponics in a flexible, budget-friendly way.

plant biology↗

bioRxiv2019

Anabolic SIRT4 exerts retrograde control over TORC1 signalling by glutamine sparing in the mitochondria

Anabolic and catabolic signalling mediated via mTOR and AMPK have to be intrinsically coupled to mitochondrial functions for maintaining homeostasis and mitigate cellular/organismal stress. Although, glutamine is known to activate mTOR, if/how differential mitochondrial utilization of glutamine impinges on mTOR signalling is less explored. Mitochondrial SIRT4, which unlike other sirtuins is induced in a fed state, is known to inhibit catabolic signalling/pathways through AMPK-PGC1a/SIRT1-PPARa axis and negatively regulate glutamine metabolism via TCA cycle. However, physiological significance of SIRT4 functions during a fed state is still unknown. Here, we establish SIRT4 as key anabolic factor that activates TORC1 signalling and regulates lipogenesis, autophagy and cell proliferation. Mechanistically, we demonstrate that the ability of SIRT4 to inhibit anaplerotic conversion of glutamine to -ketoglutarate potentiates TORC1. Interestingly, we also show that mitochondrial glutamine sparing or utilization is critical for differentially regulating TORC1 under fed and fasted conditions. Moreover, we conclusively show that differential expression of SIRT4 during fed and fasted states is vital for coupling mitochondrial energetics and glutamine utilization with anabolic pathways. These significant findings also illustrate that SIRT4 integrates nutrient inputs with mitochondrial retrograde signals to maintain a balance between anabolic and catabolic pathways.

physiology↗