VP&S Institutional Cores are charged with providing foundational and cutting-edge services to researchers across biomedical disciplines. These services enable researchers to incorporate advances in microscopy, cytometry, -omics technologies, informatics, and other disciplines into their research, regardless of their specific background or field of study.
To enable VP&S Core Facilities to remain at the forefront of technical developments and ensure researchers have access to the latest technologies, Innovation Awards are made annually on a competitive basis. These awards provide funding for cores to develop and optimize new state-of-the-art techniques, with the goal of advancing technologies beyond what is currently available elsewhere. The Awards aim to drive significant advances and innovations in core facility services, and also to foster collaborations between cores and investigator laboratories that may be experimenting with new technologies.
PI: Charles Karan
The fundamental mission of the High-Throughput Screening (HTS) Core Facility is the development, implementation, execution, and analysis of innovative high throughput screens for the community. The HTS Core possess a large collection of small molecules that are used in the execution of screens. The collection is made up of both bioactive compounds (~8000 compounds, including FDA approved drug collections) and diversity compounds (~270,000 “random” small molecules with no known predefined biological targets).
We propose a novel pooled screening methodology for screening large diversity collections, which will lower the cost and increase the speed with which large collections of small molecules can be profiled. To reach this end, this proposal will develop software to generate complex pooled screening assays and software to analyze and interpret the results.
The development and implementation of this methodology for pooled small molecule screens, will open normally expensive, large high throughput screening campaigns to more faculty.
PI: Robert Grassucci
The Columbia University Cryo-Electron Microscopy Center (CEC)’s mission is to enable Columbia University scientists to understand molecular structures fundamental to the function of all biological processes. The CEC provides training and access to the advanced instrumentation, data collection capacity, and processing support required to incorporate cryo-electron microscopy (cryo-EM) into their studies.
To better serve our users and improve safety, we propose the implementation of recently demonstrated tools for next-generation sample preparation techniques in cryo-EM. Through the development and innovation outlined in this proposal, Columbia researchers will have access to unmatched technological capabilities and the potential to make discoveries previously unattainable, all while eliminating potential hazards.
PI: Mu Yang
The Mouse Neurobehavior Core provides a behavioral testing facility operated by scientists with a strong expertise in translational behavioral science, enabling experiments needed to characterize many neurological diseases and evaluate the efficacy of experimental therapeutics.
A common critique of virtually all animal behavioral tasks is that they involve distilling highly complex patterns of action into a small subset of quantifiable readouts. This traditionally requires highly trained human observers to spend numerous hours scoring behaviors, which can be impractical for the study of diseases that develop symptoms at unpredictable times. Recently, a powerful machine learning-based method for analyzing rodent behavior was developed by Robert Datta’s lab at Stanford called motion sequencing or “MoSeq.” MoSeq provides a powerful means to merge classic behavioral assessments with comprehensive and agnostic AI-based behavioral identification. MoSeq can account for more of the actions that an animal performs than was previously possible, without having to make assumptions as to the nature of any given behavioral effect a priori. Successful implementation of MoSeq will therefore improve the throughput and reliability of behavioral assessments and benefit investigators in the fields of neuroscience, psychiatry, cancer research, neurology, environmental health, pediatrics, pathology, synthetic biology, and many more.
PIs: Howard Lieberman, Hong-Jian Wei
The Radiation Research Core provides services to a wide spectrum of investigators, whose research interests span from defining basic molecular and cellular mechanisms of the DNA damage response to pre-clinical translational studies that focus directly on optimization of radiotherapy ultimately for treatment of cancer patients.
This proposal focuses on the SARRP 200, with the intended establishment of a formalized quality assurance program for usage and significant expansion of advanced-imaging based radiotherapy in the Radiation Research Core, through collaborative efforts with the Oncology Precision Therapeutics and Imaging Core and the Columbia University PET Center. The focus will be on the development of new methodologies to combine MRI and PET, in addition to CT, with irradiation to generate novel advanced imaging-based radiotherapy services. The intended expansion of the novel advanced-imaging based radiotherapy service will allow more detailed investigations of biological processes, disease progression, and response to unique treatment, with the potential for greater translational applicability to a broader range of both pre-clinical and clinical investigations.
Single Cell Core
PIs: Peter Sims, Erin Bush
The Single Cell Core offers experimental and computational pipelines for single-cell and single-nucleus RNA-seq (scRNA-seq and snRNA-seq), single-nucleus ATAC-seq (snATAC-seq), and a multiomic workflow for joint snRNA/ATAC-seq from the same individual nuclei. While we have experienced significant growth since our launch, the vast majority of samples we process are basic research samples with only a handful of clinical samples. This is largely due to the logistical difficulty in procuring clinical samples within our operating hours. Surgery times are unpredictable, and the tissue still needs to be dissociated into live single cells for delivery to the core. In order to better serve the many uncaptured clinical samples on campus, we need an additional workflow that allows more flexibility in processing start time. Our application is for funding to implement a new single cell workflow to address these issues.