Biology subjects

Hodge, J.

Publications and source records attributed to Hodge, J..

4 recordsLinked to original sources

bioRxiv2025

The "Grove-First" Framework: Starting in the Grove to Find Therapies for Huanglongbing

Citrus greening disease, also known as huanglongbing (HLB), is the most serious vector-borne bacterial disease of citrus world-wide1,2. There is an immediate global need to provide the citrus industry with relief from HLB and a return to profitable citrus production. Standard screening methods for HLB therapeutic treatments typically involve various laboratory-based assays to select treatments with antimicrobial properties3, which then advance to greenhouse and eventually field testing in a workflow that takes multiple years. Unlike traditional lab-first screening, we present a design of experiments framework4,5, referred to as Grove-First, that rapidly screens treatments with regulatory-friendly profiles in commercial citrus groves using trunk injection to select treatments that improve tree health and fruit yield over the course of a single growing season. Using this framework, we identified candidate treatments with effects comparable to or better than the standard oxytetracycline (OTC) on visual tree-health and/or yield indices in an initial screen of HLB-positive 8-year-old Valencia sweet orange trees. Expanded trials in commercial citrus groves allowed us to validate the initial screening results at other locations and in other citrus varieties. Grove-First rapidly accelerated the identification and large-scale field testing of HLB therapies, some of which are available for growers to use immediately and others that require further field testing and/or regulatory actions.

plant biology↗

bioRxiv2024

The role of phosphorylation and dephosphorylation in the regulation of Rubisco activase

Rubisco activase is an ATP-dependent chaperone that facilitates dissociation of inhibitory sugar phosphates from the catalytic sites of ribulose-1,5-bisphosphate carboxylase/oxygenase during photosynthesis. In Arabidopsis, Rubisco activase is negatively regulated by dark-dependent phosphorylation of threonine 78. The prevalence of threonine 78 in Rubisco activase was investigated across sequences from 91 plant species, finding 29 ([~]32%) species shared a threonine in the same position. Analysis of seven C3 species with an antibody raised against a threonine 78 phospho-peptide demonstrated that this position is phosphorylated in multiple genera. However, light-dependent dephosphorylation of threonine 78 was observed only in Arabidopsis. Further, phosphorylation of threonine 78 could not be detected in any of the four C4 grass species examined. The results suggest that despite conservation of threonine 78 in Rubisco activase from a wide range of species, a regulatory role for phosphorylation at this site is more limited. This provides a case study for how variation in post-translational regulation can amplify functional divergence across the phylogeny of plants beyond what is explained by sequence variation in a metabolically important protein.

plant biology↗

bioRxiv2020

Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells

Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. This approach may still be limited by the presence of immunosuppressive myeloid populations. Here we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. Treatment of xenograft tumors resulted in PD-L1 dependent tumor growth inhibition. PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. The clinical study of PD-L1 CAR haNKs is warranted.

immunology↗

bioRxiv2017

Mutations In Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands Of Dendritic Growth And Synaptic Integrity

Mutations in the Golgi SNARE protein Membrin (encoded by the GOSR2 gene) cause progressive myoclonus epilepsy (PME). Membrin is a ubiquitously important protein mediating ER-to-Golgi membrane fusion, and hence it is unclear how these mutations result in a disorder restricted to the nervous system. Here we use a multi-layered strategy to elucidate the consequences of Membrin mutations from protein to neuron. We show that the pathogenic mutations cause partial reductions in SNARE-mediated membrane fusion. Importantly, these alterations were sufficient to profoundly impair dendritic growth in novel Drosophila models of GOSR2-PME. We also observed axonal trafficking abnormalities in this model, as well as synaptic malformations, trans-synaptic instability and hyperactive synaptic transmission. Our study highlights how dendritic growth is vulnerable even to subtle secretory pathway deficits, uncovers a previously uncharacterized role for Membrin in synaptic function, and provides a comprehensive explanatory basis for genotype-phenotype relationships in GOSR2-PME.

neuroscience↗