Biology subjects

Jacques, R.

Publications and source records attributed to Jacques, R..

2 recordsLinked to original sources

bioRxiv2022

Photoelectrochemical imaging of action potentials for single cardiomyocytes through contact force manipulation of organoids

Accurate monitoring of cardiomyocyte action potentials (APs) is essential to understand disease propagation and for trials of novel therapeutics. Patch clamp techniques offer gold standard measurements in this field, but are notoriously difficult to operate and only provide measurements of a single cell. Here we propose photoelectrochemical imaging (PEI), in conjunction with a setup for controlling the contact force between the cardiomyocyte organoids and the sensor surface, for measuring APs with high sensitivity. The method was validated through the use of drugs, and the results successfully visualized the expected electrophysiological changes to the APs. PEI allows for several cells to be monitored simultaneously, opening further research to the electrophysiological interactions of adjoining cells. This method expands the applications of PEI to three-dimensional geometries and provides the fields of stem cell research, drug trials and heart disease modelling with an invaluable tool to further investigate the role of APs.

biophysics↗

bioRxiv2019

Accelerating functional gene discovery in osteoarthritis

Osteoarthritis causes debilitating pain and disability, resulting in a huge socioeconomic burden, yet no drugs are available that prevent disease onset or progression. Here, we develop, validate and use rapid-throughput imaging techniques to identify abnormal joint phenotypes in unselected mutant mice generated by the International Knockout Mouse Consortium. We identify 14 genes with functional involvement in osteoarthritis pathogenesis, including the homeobox gene Pitx1, and functionally characterize 6 candidate human osteoarthritis genes in mouse models. We demonstrate sensitivity of the methods by identifying age-related degenerative joint damage in wild-type mice. Finally, we generate mutant mice with an osteoarthritis-associated polymorphism in the Dio2 gene by Crispr/Cas9 genome editing and demonstrate a protective role in disease onset with public health implications. This expanding resource of unselected mutant mice will transform the field by accelerating functional gene discovery in osteoarthritis and offering unanticipated drug discovery opportunities for this common and incapacitating chronic disease.

genetics↗