Biology subjects

Bacon, J.

Publications and source records attributed to Bacon, J..

2 recordsLinked to original sources

bioRxiv2018

Utilisation of the Prestwick Chemical Library (R) to identify drugs that inhibit the growth of Mycobacteria

Tuberculosis (TB) is an infectious bacterial disease that kills approximately 1.3 million people every year. Despite global efforts to reduce both the incidence and mortality associated with TB, the emergence of drug resistant strains has slowed any progress made towards combating the spread of this deadly disease. The current TB drug regimen is inadequate, takes months to complete and poses significant challenges when administering to patients suffering from drug resistant TB. New treatments that are faster, simpler and more affordable are urgently required. Arguably, a good strategy to discover new drugs is to start with an old drug. Here, we have screened a library of 1200 FDA approved drugs from the Prestwick Chemical library (R) using a GFP microplate assay. Drugs were screened against GFP expressing strains of Mycobacterium smegmatis and Mycobacterium bovis BCG as surrogates for Mycobacterium tuberculosis, the causative agent of TB in humans. We identified several classes of drugs that displayed antimycobacterial activity against both M. smegmatis and M. bovis BCG, however each organism also displayed some selectivity towards certain drug classes. Variant analysis of whole genomes sequenced for resistant mutants raised to florfenicol, vanoxerine and pentamidine highlight new pathways that could be exploited in drug repurposing programmes.

microbiology↗

bioRxiv2018

A high-throughput method for unbiased quantitation and categorisation of nuclear morphology

The physical arrangement of chromatin in the nucleus is cell type and species specific. This is particularly evident in sperm, in which most of the cytoplasm has been lost; the shape of the nucleus reflects the shape of the cell. Mice have distinctive falciform ( hook shaped) sperm heads and nuclei. Quantification of the differences in shape variation between mouse species and lines often relies on manual measurement and classification that leads to subjective results, making comparisons within and between samples difficult.\n\nWe have developed an analysis program for assessing the morphology of asymmetric nuclei, and characterised the sperm of mice from a range of inbred, outbred and wild-derived mouse lines. We find that laboratory lines have elevated sperm shape variability both within and between samples in comparison to wild-derived inbred lines, and that sperm shape in the F1 offspring of CBA and C57Bl6J lines is subtly affected by the direction of the cross.\n\nHierarchical clustering can distinguish distinct sperm shapes with greater efficiency and reproducibility than even experienced manual assessors. We quantified the range of morphological defects in the inbred BALB/c line, demonstrating we can identify different morphological subgroups. This approach has applications for studies of sperm development, infertility and toxicology.

genomics↗