MoCeIS-DCL: Planning Workshops for Synthesis of Massively Parallel Assays and Molecular Physiology

A diverse group of experimentalists, theorists, and computational experts will meet to design a communication framework that will maximize data sharing and integration and therefore current investments in research in the molecular biosciences. Workshop attendees will be tasked with a challenging question: how can one assemble the enormous amounts of data produced by distinct technologies, to answer apparently unrelated questions, so that one might see something beyond what the original experiments that produced the data sought to explore?

Is there a way to synthesize the data acquired in distinct, individually focused experiments in such a way that one may obtain a global understanding of how multiple cellular processes are coordinately orchestrated? Could one then understand how distinct processes communicate, or regulate each other across multiple spatial, temporal, and energetic scales?

A strategy to answer these questions can significantly increase the information one can extract from experimental data, and will ensure the participation of diverse investigators with their distinct perspectives.

An unassembled mosaic of molecular physiology lies waiting to be synthesized from Massively Parallel (MP) Assays and high-throughput (HT) experiments, which have revolutionized molecular and cellular biology over the past decade. Three technologies underlie the hundreds of variants of these assays: Next-Generation Sequencing (NGS), mass spectrometry, and to a lesser extent, fluorescence.

NGS-based MP assays, for example, can measure nearly all aspects of transcription, translation, and RNA degradation – from the location of every genome-bound transcription factor, DNA and RNA polymerase, every transcriptome-bound ribosome and ribosome bound factor at each stage of transcription and translation at nucleotide resolution, and the relative abundance of each mRNA. Mass spectrometry can report on interacting cellular components as well as their structural properties, while fluorescence techniques can monitor the real time location and kinetics of transcription and translation within cells.

When coupled with pulse-chase strategies or high-throughput mutagenesis, these techniques can measure the rates of subcellular processes, detect essential molecular interactions, and characterize connections between genotype and phenotype. Thus, combining the nucleotide resolution of NGS-based techniques with the compositional and structural information from mass spec, and the spatio-temporal measurements from fluorescence, provides an opportunity for a multi-dimensional mosaic of molecular physiology to be created and synthesized with the quantitative and physical approaches characterizing NSF-MCB funded researchers.

Furthermore, advances in artificial intelligence offers the opportunity to accelerate synthesis from these diverse datasets. A series of workshops to identify how the community can most efficiently use these data to promote synthesis will be held.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.