Biology subjects

Withers, J.

Publications and source records attributed to Withers, J..

3 recordsLinked to original sources

bioRxiv2025

Salicylic Acid Engages Central Metabolic Regulators SnRK1 and TOR to Govern Immunity by Differential Phosphorylation of NPR1

Immunity is a delicate balance between combating infection and preserving the metabolic functions vital for host survival. However, the mechanisms by which immune responses are coordinated with cellular metabolism remain largely unknown. Here, we show that NONEXPRESSER OF PR GENES 1 (NPR1), the central plant immune regulator of salicylic acid (SA)-mediated defense responses, is controlled by a cascade of posttranslational modifications (PTMs) involving two master nutrient-sensing kinases. Under normal growth conditions, TARGET OF RAPAMYCIN (TOR) inhibits NPR1 through phosphorylation at Ser-55/59. During defense responses, elevated SA enhances SNF1-RELATED KINASE 1 (SnRK1) activity, which in turn inhibits TOR signaling and phosphorylates NPR1 at Ser-557. This phosphorylation event activates NPR1 and facilitates its subsequent PTMs. Together, our results reveal an integral role of SA (the active metabolite of aspirin) in controlling central metabolic regulators SnRK1 and TOR to coordinate immune responses and growth through antagonistic modifications of NPR1.

plant biology↗

bioRxiv2024

ArborSim: Articulated, branching, OpenSim routing for constructing models of multi-jointed appendages with complex muscle-tendon architecture

Computational models of musculoskeletal systems are essential tools for understanding how muscles, tendons, bones, and actuation signals generate motion. In particular, the OpenSim family of models has facilitated a wide range of studies on diverse human motions, clinical studies of gait, and even non-human locomotion. However, biological structures with many joints, such as fingers, necks, tails, and spines, have been a longstanding challenge to the OpenSim modeling community, especially because these structures comprise numerous bones and are frequently actuated by extrinsic muscles that span multiple joints--often more than three--and act through a complex network of branching tendons. Existing model building software, typically optimized for limb structures, makes it difficult to build OpenSim models that accurately reflect these intricacies. Here, we introduce ArborSim, customized software that efficiently creates musculoskeletal models of highly jointed structures and can build branched muscle-tendon architectures. We used ArborSim to construct toy models of articulated structures to determine which morphological features make a structure most sensitive to branching. By comparing the joint kinematics of models constructed with branched and parallel muscle-tendon units, we found that the number of tendon branches and the number of joints between branches are most sensitive to branching modeling method--notably, the differences between these models showed no predictable pattern with increased complexity. As the proportion of muscle increased, the kinematic differences between branched and parallel models units also increased. Our findings suggest that stress and strain interactions between distal tendon branches and proximal tendon and muscle greatly affect the overall kinematics of a musculoskeletal system. By incorporating complex muscle-tendon branching into OpenSim models using ArborSim, we can gain deeper insight into the interactions between the axial and appendicular skeleton, model the evolution and function of diverse animal tails, and understand the mechanics of more complex motions and tasks.

biophysics↗

bioRxiv2019

An oomycete RXLR effector triggers antagonistic plant hormone crosstalk to suppress host immunity

Understanding the mechanisms through which pathogens alter plant cell networks is essential for understanding plant-pathogen interactions and will inform efforts to reduce crop diseases. Oomycetes secrete diverse effector proteins into plant cells. The mechanisms through which these effectors promote virulence are largely unknown. We show that the HaRxL10 effector protein from the Arabidopsis thaliana pathogen Hyaloperonospora arabidopsidis (Hpa) targets a transcriptional repressor (JAZ3) involved in jasmonic acid (JA) signalling. This manipulation activates a regulatory cascade that inhibits salicylic acid (SA) signalling, which normally restricts Hpa infection. This virulence mechanism is functionally equivalent to but mechanistically distinct from activation of the antagonistic JA-SA hormone crosstalk by the bacterial JA-mimicking toxin coronatine and by bacterial Type III effectors. These results reveal a key role for JAZ3 in plant immunity and emphasize that JA-SA crosstalk is an Achilles heel in the plant immune system, vulnerable to manipulation by diverse microbes.

plant biology↗