Biology subjects

Jennings, J.

Publications and source records attributed to Jennings, J..

4 recordsLinked to original sources

bioRxiv2021

Colletotrichum higginsianum effectors exhibit cell to cell hypermobility in plant tissues and modulate intercellular connectivity amongst a variety of cellular processes

Multicellular organisms exchange information and resources between cells to co-ordinate growth and responses. In plants, plasmodesmata establish cytoplasmic continuity between cells to allow for communication and resource exchange across the cell wall. Some plant pathogens use plasmodesmata as a pathway for both molecular and physical invasion. However, the benefits of molecular invasion (cell-to-cell movement of pathogen effectors) are poorly understood. To begin to investigate this and identify which effectors are cell-to-cell mobile, we performed a live imaging-based screen and identified 15 cell-to-cell mobile effectors of the fungal pathogen Colletotrichum higginsianum. Of these, 6 are "hypermobile", showing cell-to-cell mobility greater than expected for a protein of its size. We further identified 3 effectors that can indirectly modify plasmodesmal aperture. Transcriptional profiling of plants expressing hypermobile effectors implicate them in a variety of processes including senescence, glucosinolate production, cell wall integrity, growth and iron metabolism. However, not all effectors had an independent effect on virulence. This suggests a wide range of benefits to infection gained by the mobility of C. higginsianum effectors that likely interact in a complex way during infection.

plant biology↗

bioRxiv2020

Automated tracking of S. pombe spindle elongation dynamics

The mitotic spindle is a microtubule-based machine that pulls the two identical sets of chromosomes to opposite ends of the cell during cell division. The fission yeast Schizosaccharomyces pombe is an important model organism for studying mitosis due to its simple, stereotyped spindle structure and well-established genetic toolset. S. pombe spindle length is a useful metric for mitotic progression, but manually tracking spindle ends in each frame to measure spindle length over time is laborious and can limit experimental throughput. We have developed an ImageJ plugin that can automatically track S. pombe spindle length over time and replace manual or semi-automated tracking of spindle elongation dynamics. Using an algorithm that detects the principal axis of the spindle and then finds its ends, we reliably track the length and angle of the spindle as the cell divides. The plugin integrates with existing ImageJ features, exports its data for further analysis outside of ImageJ, and does not require any programming by the user. Thus, the plugin provides an accessible tool for quantification of S. pombe spindle length that will allow automatic analysis of large microscopy data sets and facilitate screening for effects of cell biological perturbations on mitotic progression.

cell biology↗

bioRxiv2020

Chemical Stabilization of the HIV-1 Capsid Results in Efficient HIV-1 Reverse Transcription in vitro

A defining activity of retroviruses is reverse transcription, the process during which the viral genomic RNA is converted into the double strand DNA required for virus replication. Reverse transcriptase (RT), the viral enzyme responsible for this process, was identified in 1970 by assaying permeabilized retrovirus particles for DNA synthesis in vitro. Such reactions are inefficient with only a small fraction of viral genomes being converted to full-length double strand DNA molecules, possibly owing to disruption of the structure of the viral core. Here we show that reverse transcription in purified HIV-1 cores is enhanced by the addition of the capsid-binding host cell metabolite inositol hexakisphosphate (IP6). IP6 potently enhanced full-length minus strand synthesis, as did hexacarboxybenzene (HCB) which also stabilizes the HIV-1 capsid. Both IP6 and HCB stabilized the association of the viral CA and RT proteins with HIV-1 cores. In contrast to the wild type, cores isolated from mutant HIV-1 particles containing intrinsically hyperstable capsids exhibited efficient reverse transcription in the absence of IP6, further indicating that the compound promotes reverse transcription by stabilizing the viral capsid. Our results show that stabilization of the HIV-1 capsid permits efficient reverse transcription in HIV-1 cores, providing a sensitive experimental system for analyzing the functions of viral and host cell molecules and the role of capsid disassembly (uncoating) in the process. IMPORTANCEHIV-1 infection requires reverse transcription of the viral genome. While much is known about the biochemistry of reverse transcription from simplified biochemical reactions, reverse transcription during infection takes place within a viral core. However, endogenous reverse transcription reactions using permeabilized virions or purified viral cores have been inefficient. Using viral cores purified from infectious HIV-1 particles, we show that efficient reverse transcription is achieved in vitro by addition of the capsid-stabilizing metabolite inositol hexakisphosphate. Enhancement of reverse transcription was linked to the capsid-stabilizing effect of the compound, consistent with the known requirement for an intact or semi-intact viral capsid for HIV-1 infection. Our results establish a biologically relevant system for dissecting the function of the viral capsid and its disassembly during reverse transcription. The system may also prove useful for mechanistic studies of emerging capsid-targeting antiviral drugs.

microbiology↗

bioRxiv2020

BioDynaMo: an agent-based simulation platform for scalable computational biology research

MotivationAgent-based modeling is an indispensable tool for studying complex biological systems. However, existing simulators do not always take full advantage of modern hardware and often have a field-specific software design. ResultsWe present a novel simulation platform called BioDynaMo that alleviates both of these problems. BioDynaMo features a general-purpose and high-performance simulation engine. We demonstrate that BioDynaMo can be used to simulate use cases in: neuroscience, oncology, and epidemiology. For each use case we validate our findings with experimental data or an analytical solution. Our performance results show that BioDynaMo performs up to three orders of magnitude faster than the state-of-the-art baseline. This improvement makes it feasible to simulate each use case with one billion agents on a single server, showcasing the potential BioDynaMo has for computational biology research. AvailabilityBioDynaMo is an open-source project under the Apache 2.0 license and is available at www.biodynamo.org. Instructions to reproduce the results are available in supplementary information. Contactlukas.breitwieser@inf.ethz.ch, a.s.hesam@tudelft.nl, omutlu@ethz.ch, r.bauer@surrey.ac.uk Supplementary informationAvailable at https://doi.org/10.5281/zenodo.4501515.

systems biology↗