Biology subjects

Ross, J. J.

Publications and source records attributed to Ross, J. J..

5 recordsLinked to original sources

bioRxiv2026

Evolution of an Aurora Kinase A Inhibitor from an Essential tRNA Synthetase

Gene duplication is a major driver of evolution, yet how it generates fundamentally new molecular functions remains poorly understood. Here, we show how such novelty arose in KLMT-1, a selfish toxin that causes genetic incompatibilities in Caenorhabditis tropicalis. KLMT-1 evolved via duplication of an essential tRNA synthetase but, strikingly, lost its ancestral role in tRNA biology and translation. Instead, KLMT-1 localizes to centrosomes, where it targets Aurora kinase A (AIR-1). This innovation is mediated by a three-amino acid insertion that extends a {beta}-hairpin loop, enabling electrostatic interaction with a regulatory interface on the kinase. Our results demonstrate how changes in selective pressure, combined with minimal modifications in neutrally evolving regions, allow duplicated proteins to access new functional space and evolve entirely new molecular activities.

evolutionary biology↗

bioRxiv2024

A regulatory module driving the recurrent evolution of irreducible molecular complexes.

To sustain life, molecular complexes require the concerted action of multiple proteins, each relying on one another to perform intricate tasks. However, how such interdependent protein interactions evolve in the first place is poorly understood. To address this, we investigated the origins of a group of fast-evolving genetic parasites--toxin-antidote elements--which boil down this dilemma to a simple question: what came first, the toxin or the antidote? By integrating quantitative genetics, biochemistry, and evolutionary genomics, we discovered that toxins and antidotes can arise simultaneously through the duplication of a regulatory module comprising an F-box protein in linkage to its substrate. Our findings provide one solution to the recurrent emergence of mutual dependence in protein complexes and illustrate in detail how complexity can swiftly arise from simplicity.

genomics↗

bioRxiv2023

Sustained In Vivo Perfusion of a Re-Endothelialized Tissue Engineered Kidney Graft in a Human-Scale Animal Model

IntroductionDespite progress in whole-organ decellularization and recellularization, maintaining long-term perfusion in vivo remains a hurdle to realizing clinical translation of bioengineered kidney grafts. The objectives for the present study were to define a threshold glucose consumption rate (GCR) that could be used to predict in vivo graft hemocompatibility and utilize this threshold to assess the in vivo performance of clinically relevant decellularized porcine kidney grafts recellularized with human umbilical vein endothelial cells (HUVECs). Materials and MethodsTwenty-two porcine kidneys were decellularized and 19 were re-endothelialized using HUVECs. Functional revascularization of control decellularized (n=3) and re-endothelialized porcine kidneys (n=16) was tested using an ex vivo porcine blood flow model to define an appropriate metabolic glucose consumption rate (GCR) threshold above which would sustain patent blood flow. Re-endothelialized grafts (n=9) were then transplanted into immunosuppressed pigs with perfusion measured using angiography post-implant and on days 3 and 7 with 3 native kidneys used as controls. Patent recellularized kidney grafts underwent histological analysis following explant. ResultsThe glucose consumption rate of recellularized kidney grafts reached a peak of 41.3{+/-}10.2 mg/hour at 21{+/-}5 days, at which point the grafts were determined to have sufficient histological vascular coverage with endothelial cells. Based on these results, a minimum glucose consumption rate threshold of 20 mg/hour was set. The revascularized kidneys had a mean perfusion percentage of 87.7{+/-}10.3%, 80.9{+/-}33.1%, and 68.5{+/-}38.6% post-reperfusion on Days 0, 3 and 7, respectively. The 3 native kidneys had a mean post-perfusion percentage of 98.4{+/-}1.6%. These results were not statistically significant. ConclusionThis study is the first to demonstrate that human-scale bioengineered porcine kidney grafts developed via perfusion decellularization and subsequent re-endothelialization using HUVEC can maintained patency with consistent blood flow for up to 7 days in vivo. These results lay the foundation for future research to produce human-scale recellularized kidney grafts for transplantation.

bioengineering↗

bioRxiv2020

Scalable, rapid and highly sensitive isothermal detection of SARS-CoV-2 for laboratory and home testing

Global efforts to combat the Covid-19 pandemic caused by SARS-CoV-2 still heavily rely on RT-qPCR-based diagnostic tests. However, their high cost, moderate throughput and reliance on sophisticated equipment limit widespread implementation. Loop-mediated isothermal amplification after reverse transcription (RT-LAMP) is an alternative detection method that has the potential to overcome these limitations. We present a rapid, robust, sensitive and versatile RT-LAMP based SARS-CoV-2 detection assay. Our forty-minute procedure bypasses a dedicated RNA isolation step, is insensitive to carry-over contamination, and uses a hydroxynaphthol blue (HNB)-based colorimetric readout, which allows robust SARS-CoV-2 detection from various sample types. Based on this assay, we have substantially increased sensitivity and scalability by a simple nucleic acid enrichment step (bead-LAMP), established a pipette-free version for home testing (HomeDip-LAMP), and developed open source enzymes that can be produced in any molecular biology setting. Our advanced, universally applicable RT-LAMP assay is a major step towards population-scale SARS-CoV-2 testing.

molecular biology↗

bioRxiv2019

Trehalose 6-phosphate Controls Seed Filling by Inducing Auxin Biosynthesis

Plants undergo several developmental transitions during their life cycle. One of these, the differentiation of the young embryo from a meristem-like structure into a highly-specialized storage organ, is vital to the formation of a viable seed. For crops in which the seed itself is the end product, effective accumulation of storage compounds is of economic relevance, defining the quantity and nutritive value of the harvest yield. However, the regulatory networks underpinning the phase transition into seed filling are poorly understood. Here we show that trehalose 6-phosphate (T6P), which functions as a signal for sucrose availability in plants, mediates seed filling processes in seeds of the garden pea (Pisum sativum), a key grain legume. Seeds deficient in T6P are compromised in size and starch production, resembling the wrinkled seeds studied by Gregor Mendel. We show also that T6P exerts these effects by stimulating the biosynthesis of the pivotal plant hormone, auxin. We found that T6P promotes the expression of the auxin biosynthesis gene TRYPTOPHAN AMINOTRANSFERASE RELATED2 (TAR2), and the resulting effect on auxin levels is required to mediate the T6P-induced activation of storage processes. Our results suggest that auxin acts downstream of T6P to facilitate seed filling, thereby providing a salient example of how a metabolic signal governs the hormonal control of an integral phase transition in a crop plant.

plant biology↗