bioRxiv ScienceSearch

Biology subjects

Porter, D. A.

Publications and source records attributed to Porter, D. A..

2 recordsLinked to original sources

The Forget-Me-Not dHCP study: 7 Tesla high resolution diffusion imaging in the unfixed post-mortem neonatal brain

Diffusion MRI of the neonatal brain allows investigation of the organisational structure of maturing fibres during brain development. Post-mortem imaging has the potential to achieve high resolution by using long scan times, enabling precise assessment of small structures. The Forget-Me-Not study, part of the Developing Human Connectome Project (dHCP), aims to acquire and publicly distribute high-resolution diffusion MRI data for unfixed post-mortem neonatal brain at 7T with a custom-built head coil. This paper describes how the study addressed logistical, technical and ethical challenges relating to recruitment pipeline, care pathway, tissue preservation, scan setup and protocol optimisation. Results from the first subject recruited to the study demonstrate high-quality diffusion MRI data. Preliminary voxel-wise and tractography-based analyses are presented for the cortical plate, subplate and white matter pathways, with comparison to age-matched in vivo dHCP data. These results demonstrate that high quality post-mortem data can be acquired and provide a sensitive means to explore the developing human brain, as well as altered diffusion properties consistent with post-mortem changes, at high resolution.

bioengineering

Highly multiplexed quantitative phosphosite assay for biology and preclinical studies

Reliable methods to quantify dynamic signaling changes across diverse pathways are needed to better understand the effects of disease and drug-treatment in cells and tissues but are presently lacking. Here we present SigPath, a targeted mass spectrometry (MS) assay that measures 284 phosphosites in 200 phosphoproteins of biological interest. SigPath probes a broad swath of signaling biology with high throughput and quantitative precision. We applied the assay to investigate changes in phospho-signaling in drug-treated cancer cell lines, breast cancer preclinical models and human medulloblastoma tumors. In addition to validating previous findings, SigPath detected and quantified a large number of differentially regulated phosphosites newly associated with disease models and human tumors at baseline or with drug perturbation. Our results highlight the potential of SigPath to monitor phosphoproteomic signaling events and to nominate mechanistic hypotheses regarding oncogenesis, response and resistance to therapy.

cancer biology