Single cell multi-omics sequencing platform to understand the building blocks of life.

It is necessary to clearly resolve and describe living systems at a cellular resolution, in order to understand the rules of life, to understand health and increase healthy lifespans, or to improve sustainability in agriculture. This presents a major challenge as organisms are often composed of huge numbers of cells with very different properties that have complex interactions with each other, and until recently there was no technology that would allow such resolution.

This single cell multi-omics phenotyping platform allows cells from any tissue or organism to be explored at a single cell level. The platform makes it possible to take a large collection of cells (e.g. a tissue sample, biopsies, cells treated with specific compounds) and give each cell a unique barcode label before determining its properties. Each cell can then be explored for a range of molecular properties such as determining the sequence or structure of the genome, the genes that are expressed in the cell, and the proteins expressed in the cell or at the surface of the cell.

The proposed platform will allow researchers to explore the intricate cellular architecture that underlies how traits are determined in complex organisms, and shed light on how they evolved. The range of research facilitated by this platform addresses questions including: how communication behaviour is encoded in the brain; how the body controls motor functions and what goes wrong in motor neuron disease; how genetic mechanisms influence development, fertility and parental provisioning; how organisms adapt to extreme conditions over evolution; neural control of nest building in birds; the role of genome structure in directing the forms tissues or animal bodies take; cancer progression and the effect of cancer drugs on the body; how the immune system functions in health and disease; normal and abnormal neurodevelopment; improving crop production; and developing new computational methods for data analyses. This cutting-edge technology platform would therefore facilitate a massive step forward in a diverse range of key research areas, that will impact crucial research fields across evolution, development, physiology, behaviour, medicine, agriculture and environmental sustainability.

Single cell phenotyping has opened the door to understanding biological systems at an unprecedented level. Until recently, when trying to couple genotype to phenotype in the study of evolution, development, behaviour or health, only bulk -omics profiling approaches were possible that took the 'average properties' of a tissue or organismal state as a readout. Such averaging of properties are often misleading and in the best case only allow an understanding of some of the most dominant properties of a tissue. This does not allow the resolution necessary for a true understanding of the biology of an organism during normal conditions, or the perturbations in altered states.
Single cell phenotyping has provided a step-change in many research fields, allowing us to examine the properties of each distinct cell to build a clear picture of the individual components of a tissue or organism, rather than an average of the whole. This is particularly important to understand properties of evolution, development, behaviour, and health since taking the average readout hides the plethora of important cell types and mechanisms that drive these complex processes.
The proposed single cell multi-omics phenotyping platform would allow researchers to perform all the steps required to go from conception to completion of a study. Single cell sorting, barcoding and rapid high throughput sequencing from samples from any species or tissue on this platform will facilitate a range of multi-omic phenotyping studies at an unprecedented resolution including single cell RNA expression sequencing, profiling of surface proteins, immune clonotypes, antigen specificity, CRISPR perturbation profiling and chromatin accessibility profiling (eg ATAC-seq), and many more. This platform would for the first time allow researchers at the University of St Andrews to harness this revolutionary approach and benefit from its advantages in their research in a convenient, rapid and fully controllable manner.