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ImmunoX proposes an innovative concept in collaborative sciences, seeking to keep scientists engaged in their personal missions, while sharing their methods and technologies and adding wide-sweeping value to a common database called the Data Library.
The core concept is a series of ImmunoX CoProjects located within UCSF CoLabs space to survey the immune contexture of varying degrees of “healthy” and diseased states.
The underlying hypothesis is the existence of a finite number of immunological themes of cellular composition, positioning, and gene expression patterns within normal and diseased tissues.The process of finding and exploiting them for diagnostic and therapeutic purposes benefits from a common platform and shared database. We anticipate that this form of collaboration will accelerate cures for diseases ranging from cancer to autoimmunity. We also anticipate that new discoveries of methods to exploit these immunological themes may be serendipitous, conceivably from piloting rare cases or diseases. Finding these cases requires a wide net and a pipeline that can take in large cohorts as well as new pilots.
CoProjects
A funded CoProject typically consists of a standard set of high-dimensional assays for a fixed number of samples over an approximate time period. Non-standard assays, either novel or developmental, can also be proposed, but may require external funding or an agreement to share and implement the assay within the UCSF CoLabs. All standard assays require adherence to a set of standard operating procedures (SOPs) to ensure highly consistent and high-quality data across datasets.
Day-to-day operations are managed and run through the UCSF CoLabs. As a sample comes through the pipeline, the technician processes it, while the data scientist curates and stores it in the Data Library. A set embargo period is placed on the data to give the investigator and his/her team a “first-pass” opportunity to mine it and make discoveries. After the embargo period is lifted, the data becomes open-access to all ImmunoX members in the Data Library for analysis and cross-comparison with other open-access datasets.
Please note: CoProjects do not fund investigator salaries or benefits, except under extraordinary circumstances.
CoProject Pilots
Pilots are defined as ≤12 cases in order to generate feasibility and diligence data for larger cohort studies, as well as for hypothesis testing and development. Pilots are usually collected within one year of start date but may be extended based on circumstance. Pilots utilize effort from current D2B and DS CoLab personnel, which are allocated by their respective CoLab Directors.
CoProjects are the funding mechanism for ImmunoX, while CoLabs are the technology and infrastructure that supports the CoProjects. CoLabs are funded by institutional support and serve a user base across the entire UCSF community, not just the CoProjects.
Unlike fragmented “cores,” which age and become obsolete over time, CoLabs revitalize the model for core resources by capitalizing on critical personnel and cutting-edge technologies, and driving collaboration across disciplines.
The model will house all CoLabs in a contiguous space and create a set of common pipelines and workflows in one centralized location. CoLabs recruit and retain world-class staff through project engagement, backstopped “tenure,” and annual operational funds. It continuously develops and invests in transformative methods and technologies.
In its current form, CoLabs comprises five functional units:
Disease to Biology CoLab: A new CoLab that specializes in consistent and high-quality human specimen processing. Technicians associated with ImmunoX CoProjects are housed here and are responsible for coordinating specimen processing and data analysis workflows with other CoLabs.
Flow Cytometry CoLab: A CoLab that integrates the existing Parnassus Flow Cytometry Core and specializes in counting, sorting, and analyzing suspensions of cells using advanced cell sorting and cytometric analyses technologies.
Biological Imaging Development CoLab: A CoLab that integrates the existing Biological Imaging Development Center and specializes in assembling, testing, and applying emerging light microscopy techniques and technologies.
Genomics CoLab: A CoLab that integrates existing but fragmented units at UCSF. It specializes in performing single-cell gene transcript sequencing and developing and deploying innovative methods for analyzing and modifying gene function.
Data Sciences CoLab: A new CoLab to develop bioinformatic frameworks for curating, storing, analyzing, and sharing access to data produced through the CoLabs pipeline. It will also house bioinformaticians and computational biologists to drive ImmunoX CoProjects.
In addition to the five CoLabs listed above, CoLab Incubators and Plug-ins are available. These integrations offer extra expertise and services to expand the scope of CoProjects. ImmunoX has partially funded all existing CoLab Incubators and Plug-ins to date to better support our expanding community.
CoProjects aims to sample across a wide spectrum of normal and diseased blood and tissues. Proposals are evaluated based on how differentially arrayed and novel the immune system’s response is in the proposed disease types compared to diseases already profiled. At this time, we encourage applicants to apply for, but are not limited to, the following immune-mediated topics:
1. Local and systemic immunity at sites of chronic infection
2. Local and systemic immunity at sites in neuroinflammation
3. Wound healing and fibrosis
4. Local and systemic immunity in autoimmunity
5. Local and systemic immunity in aging, with emphasis on wound healing and anti-cancer responses
6. Population-level variations in “normal” immune responses in blood and tissues
There is a standard 18-month embargo on data generated in the CoProjects. This timeline is negotiable based on sample enrollment and completion schedules. Following the defined embargo period, CoProjects data becomes available to other members of the ImmunoX community. Investigators who want access to a CoProject must first contact the CoProject Principal Investigator and Bakar ImmunoX ChiefStrategist. Investigators who use data on any publication must offer middle authorship to the CoProjects Principal Investigator and acknowledge ImmunoX CoProjects as a partial or full source of support.
It is highly recommended that a pilot study be completed in advance of a full proposal to determine feasibility. We also ask that the proposal include evidence of live specimen availability at UCSF from previous years of clinical records. The live specimen must be able to be transported to the D2B CoLab within 2 hours on ice. At present, CoProjects requires the investigator to either have an IRB approved at inception or use our universal ImmunoX Biospecimen IRB.
Standard assays for CoProjects include:
Diseased or adjacent normal tissue:
· 2 panels for mass cytometry (CyTOF)
Standard panels are available shown on the RFP; open channels allow for 2-3investigator-specific antibodies
· 2 pre-sorted populations for single-cell sequencing (scSeq)
Lymphocyte and non-lymphocyte or myeloid-enriched populations
· Embedded fixed-formalin paraffin-embedded (FFPE) blocks
Two 5-color immunofluorescence imaging panels or 20-color multiplex ion beam imaging (MIBI) panels (in development)
Blood
· 2 panels for mass cytometry (CyTOF)
Standard panels are available shown on the RFP; open channels allow for 2-3investigator-specific antibodies
· 2 pre-sorted populations for single-cell sequencing (ssSeq)
Lymphocyte and non-lymphocyte or myeloid-enriched populations
· 5 panels of 17-colors each for standard flow cytometry
· 5 population bulk RNA sequencing
· Organoids
· Live biopsy imaging
· Microbiome analysis
· Serum proteomics for mass spectrometry
Each of these options should be discussed with the Bakar ImmunoX Chief Strategy Officer and D2B CoLab Director prior to application. SOPs are available upon request.
Beyond the execution of standard assays,CoProjects is devoted to cultivating emerging methods and technologies in the CoLabs. These include but are not limited to:
1. Implementation of Perturb-Seq to study the diversity of “poised” states in immune cells
2. Implementation of single-cell ATAC-Seq to study chromatin states and accessibility
3. Implementation of metabolic profiling to study changes induced by external stimuli and inherent biological variations within subpopulations
4. Development of longitudinal studies of blood for people with likelihood of adverse immune reactions
5. Development of live-imaging methodologies for understanding cellular behaviors across time and space in normal and diseased tissues
6. Development of computation methods to discover hidden immune states
7. Comparision of mouse models to human datasets to validate and improve models
The ImmunoX Research Committee is responsible for reviewing and selecting CoProject Pilot proposals for funding. The primary criteria to evaluate proposals include but are not limited to:
· Proven ability to provide samples in a timely manner to the CoLabs and to process samples using standard CoProjects pipelines and assays
· Novelty of the sample type and its potential ability to illuminate new immune states not already profiled in the ImmunoX Data Library
· Novelty of non-standard assays, if applicable, with regard to their potential ability to understand new immune states
CoProject Pilot proposals are awarded one term of 1-2 years for sample acquisition, processing, and analysis. The start of a project should begin within 6 months of a decision, contingent upon sample streams and hiring and allocation of CoLabs personnel.
Potential applicants are encouraged to discuss applications with the ImmunoX Chief Strategy Officer, Vincent.Chan@ucsf.edu.
