This Shared Instrumentation Grant proposal requests $482,395 to acquire a suite of instruments to enable single-cell genomics to support research programs at Case Western Reserve University [CWRU] and the Cleveland Clinic Foundation. The instruments will be placed in an established, successful Core Facility at CWRU. Development of the Single Cell Genomics Service using these instruments, however, will be an inte- grated effort involving 3 existing Core Facilities with relevant expertise, experience and an impressive roster of instruments. The combined capacities of these Cores are essential to capitalize on a broad spectrum of geno- mics technologies required to fully exploit the potential of the requested instrument suite. The equipment will be used solely as a shared resource, under the direction of the 3 Directors of the CWRU Core Facilities who have established histories for providing high quality services and for inter-core collaboration. Leveraging the resour- ces and expertise of these 3 Core Facilities ensures the availability of the requested comprehensive array of offerings for the Single Cell Genomic Service and promises rapid equipment installation and service provision through establishment of integrated single cell workflows. Rapid implementation of the instrumentation suite will also be assured by established communication with the extensive User Communities of the 3 collaborating Core Facilities which ensures easy access to and high visibility of the new instruments and service. Establishment of single cell genomic capability will allow investigators to identify rare [disease] cells with spe- cific genomic and interaction patterns within a sample. Without these instruments, contributions and interac- tions between individual cells in tumors and cellular-based disease processes are masked by the majority of the cell population and can't be studied. The requested technology opens previously unavailable approaches to analysis of the role of population heterogeneity. Identification of genetic markers and their mechanistic inter- actions in critical cell subpopulations will play increasing roles in our understanding of disease, drug resistance, cancer diagnosis and monitoring, biomarker exploitation and targeted drug development. In addition to the unique single-cell capability the requested equipment will facilitate interrogation of very small amounts of nucleic acid, which provides the ability to conserve rare and valuable samples. It will also result in rapid and economical execution of customized expression and genotyping studies and pursuit of projects requiring ability to perform custom amplification of small targets in large sample sets. The cutting-edge capabilities of the requested instrument suite will immediately and directly benefit funded CWRU investigators and will stimulate new research capabilities. Currently, this comprehensive integrated sin- gle cell genomic technology is not available in Northeast Ohio. By bring this state of the art technology to CWRU, the Institution will strengthening its academic research infrastructure, enhance its ability to recruit more top scientists and expand its collaborations across Ohio.
Instruments will be purchased, which will allow investigators to simultaneously analyze up to 100 individual cells from a single sample for their ability to produce 1000s of gene products. Single cell analysis will iden- tify minor populations of cells within clinical specimens that carry key traits; without this analysis, contribu- tions of these minor populations cannot be detected within the large cell population. Since it is often the properties of minor population of cells that are central to understanding the progress of disease or resis- tance to therapies, this novel new analytical capacity is crucial for our progress in unravelling disease processes.
