Central Research Labs (CRL) - Space@UCSF

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Central ResearchLabs (CRL)PLAN PROPOSALCRL Subgroup Report to theParnassus Master Planning Steering CommitteeApril 27, 2018

2017 CHANCELLOR’S ANNUAL ADDRESSState of the University“Excellence”“Now is the time to start”“Impassioned engagement of theParnassus Heights-based faculty”“Incredibly exciting ideas”“World-class modern facilities”“Big and bold”

CRL SUBGROUP COMMITTEEMandate Design a new model for central lab resources Capitalizes on critical personnel and cutting-edge methods & technologies Drives collaboration across disciplines Produce high level plans for contiguous space housing all CRL components Integrates core activities into one centralized place, e.g. sample processing, highdimensional imaging, cell separation/sorting, genomic analysis Maximize impact & engagement Launch within a 2-year timeline

CRL SUBGROUP COMMITTEEMembership and ProcessNADAV AHITUV, PHDBioengineering & TherapeuticsDIANE KAYSpace & Capital PlanningPATTI MITCHELLCapital ProgramsJIMMIE YE, PHDEpidemiology & BiostatisticsVINCENT CHAN, PHDPathologyMAX KRUMMEL, PHDPathologyELIZABETH SINCLAIR, PHDResearch Resource ProgramKARIN WONGSpace StrategyERIC CHOW, PHDBiochemistry & BiophysicsTIPPI MACKENZIE, MDSurgeryMATTHEW SPITZER, PHDMicrobiology and ImmunologyHUGH COTTER, AIAOculus Architects, Inc.LINDSEY CRISWELL, MD, MPHMedicineALEX MARSON, MD, PHDMicrobiology and ImmunologySAUL VILLEDA, PHDAnatomyDAVID ERLE, MDMedicineMICHAEL MCMANUS, PHDDiabetes CenterKATHERINE YANG,PHARMD, MPHClinical PharmacySINCE JANUARY 2018: 5 committee meetings 7 task forces Website Email announcements Existing facility inventory Site visits

CRL SUBGROUP COMMITTEEChallenges Fragmented facilities SFGH Lagging investments in transformativemethods & technologies Parnassus Mission BayData sciencesGenomicsUnreliable long-term financial support Difficult to find and use coresLimits collaboration and synergiesInefficient use of space and equipmentInefficienciesInadequate institutional support for cores(9% versus 27% nationally)Retention of world-class staff

CRL SUBGROUP COMMITTEEGoals & Opportunities Rejuvenating ParnassusComplete promptly a highly-visible model for developing big and bold initiatives at Parnassus Building on Parnassus’ strengthEmphasize Parnassus’ unique strengths by exploring the biological basis of disease in transformativenew ways and by complementing resources available elsewhere Fostering collaborationEnhance a sense of community by moving beyond the traditional “core” model and facilitating the sharingof resources, expertise, and data Creating excellence, responsiveness, and sustainabilityRecruit and retain excellent people who are engaged and nimble in recognizing emergingopportunities, and who can promote the sharing of ideas and tools developed in individual labs Supporting education and training

CRL SUBGROUP COMMITTEEVisionSFGHParnassusParnassusMission Bay

CRL SUBGROUP COMMITTEEDesign ConceptA TP A R N A S S U SParnassusThe “C” is a multi-faceted representation of CoLabs: as a logomark; as an interconnectedspace of shared labs; as an open “ring of collaboration” that will mirror the eventualrejuvenation and space concept at Parnassus.

CRL SUBGROUP COMMITTEECoLabs at GANOIDSPARNASSUSFLOWCYTOMETRYCORE (PFCC)AUTOIMMUNITYBULKPOPULATIONSEQUENCINGDISEASE TOBIOLOGYHUB MAGINGDEVELOPMENTCENTER(BIDC)NONI N VA S I V GENOMICSCOMPBIOBIOINFORMATICSDATA SCIENCES/DATA LIBRARY(DS)

COLABS AT PARNASSUSBenefits to Parnassus and UCSFDramatically lower barriers for interdisciplinary collaborations Allows access to sophisticated approaches essential for cutting-edge science Especially important for early stage investigators and clinical-scientistsDrive more efficient use of costly sharable resources Reduce costs and need for space in other Parnassus projects that will follow Data sharing ensures maximizes benefits of patient-based researchReduce glaring inequities between Parnassus and MB Improve Parnassus morale and build excitement about the future of Parnassus Decrease need to travel to MB for important servicesEnable a new financial model Attract a broader range of funders Leverage large project funding to benefit the whole communityProvide a visible center for researchers at Parnassus Build a sense of community Provide new facilities and personnel for training and innovation

COLABS AT PARNASSUSSingle CoLab Use CaseDoug Gould, PhD and Scott Oakes, MDwant to use gene editing to cure inheritedforms of blindness. They are looking formouse models for assessing the efficacy ofediting a relevant target gene in the retina.Doug and Scott consult with MichaelMcManus who provides advice about suitabletools. They can develop the requiredtransgene constructs in their own labs ortravel to the MB Cell and GenomeBIOSPECIMENRESOURCESEngineering Core to work with them. ForPARNASSUSPROGRAMFLOWgeneration of transgenic mice from ESCYTOMETRYcells,Parnassus investigatorscan use either theCOREDISEASE TOGladstone core orBIOLOGYan off-campus serviceHUB shipped to Doug andprovider. Mice are thenScott, who genotype them and deliver somemice to the LARC Rederivation Core forpreservation. Therapeutic CRISPR AAVs canbe produced with help from the UCSFViraCore.SINGLE COLAB PROJECTStep 1. Doug and Scott work with theGenomics CoLab director to design theexperiment, offering new technologies that raiseimpact and often save both time and money.Step 2. The Genomics CoLab performs ESgene targeting, microinjects ES cells, helpsgenotype animals and offers a phenotypingservice via UCD liaison.Step 3. The Genomics CoLab biobanks locallyor with a UCD liaison.BIOLOGICALIMAGINGDEVELOPMENTCENTERStep 4. The Genomics CoLab produces theCRISPR AAV construct and coordinates withthe ViraCore to produce therapeutic AAV.GENOMICSDATA SCIENCES/DATA LIBRARY

COLABS AT PARNASSUSCoLabs ProjectsStep 4. BIDC personnel receives tissue slices fromD2B technician and uses multiplexed IF imagingtechniques and quantification methods to understandspatial interplay of tumor/immune cells.BIOSPECIMENRESOURCESPROGRAMDISEASE TOBIOLOGYHUBCOLABS PROJECTStep 5. Genomics personnel receives sorted tumor/immune cells from D2B technician and isolates RNA& DNA for transcriptomic & genomic sequencing oftumor/immune compartments.PARNASSUSFLOWCYTOMETRYCOREStep 1. Jocelyn works with the CoLabs director todefine pilot project of 12 ovarian samples in thepipeline. BIOS works with Jocelyn to identify,consent, and acquire tissue & blood from patients.Step 2. BIOS transfers tissue & blood to D2Btechnician. D2B technician takes a tissue slice forH&E/IF and dissociates the rest; the technician alsoisolates PBMCs from blood.Step 3. D2B technician works with PFCC personnelto reserve FACS, sort tumor/immune cells for multiomic analyses, and runs several stain panels tounderstand the immune composition.Jocelyn Chapman, MD is keen tounderstand the immune diversity ofgynecological tumors that she is obtaining inthe clinic. Like many clinician-scientists, shedoes not have her own lab with the capacityto undertake this work. Instead, she is ableto contribute tumor and blood specimensand a clinical research coordinator FTE SStep 6. Bioinformaticians receive, curate, and storeall data (including clinical) in the UCSF Data Library,and work with Jocelyn to develop analytical tools tomine the ovarian tumor dataset. Data is “freed” to allUCSF investigators after set determined time.DATA SCIENCES/DATA LIBRARY

COLABS AT PARNASSUSImpact on ResearchersImprove services for existing users of Parnassus cores PFCC (Flow Cytometry) 140 PIsBIDC (Imaging) 51 PIs, 19 departmentsCTSI CRS Sample Processing Core 59 PIsIHG Core Single Cell RNA-seq 50 PIsParnassus Center for Advanced Technology 15 PIsImmunoprofiler Flow/Sequencing and Allied Projects 25 PIsProvide on-site access to key services now only available elsewhere Nikon Imaging Center in Genentech Hall 191 PIs, 15% at ParnassusCenter for Advanced Technology in Genentech Hall 150 PIs, 15% at ParnassusTransgenic Core at Gladstone 35 UCSF PIs, 50% at ParnassusFunctional Genomics Core in Rock Hall 55 PIs, 49% at ParnassusClinical Immunology Lab at ZSFG 27 PIs, all would benefit from access to PFCCNew models for collaboration and funding Embedding trainees and staff get outstanding access to expertise and equipment without need to set up in PI’s own labUse of new 100/20 mechanism allows for support of pilot projectsFacilitates data sharing with UCSF colleagues, fundersUnlock access to transformative technologies for existing and new users Data sciences for storage and analysis of large datasets (including genomics)New imaging and single cell analysis methodsAdvanced gene editing (CRISPR and beyond)Massively parallel functional assays

COLABS AT PARNASSUSNew User AccessNew users can enter the CoLabs in one of several ways: Direct access:Access by interacting directly with the CoLabs Director. The new user will typically be the PIand the project will largely be managed by personnel determined by the Director. Sponsored access:Access through collaboration with an existing user (Sponsor). The project will largely bemanaged by personnel “linked” to the Sponsor’s existing project. Recharge/subscription access:Each CoLab will retain its traditional “core” capacities, e.g. daily users who use a singlepiece of equipment

COLABS AT PARNASSUSCoLabs OrgChartCOLABS DIRECTORD2BPFCCBIDCGENOMICSDSD2B STEERINGCOMMITTEEPFCC STEERINGCOMMITTEEBIDC STEERINGCOMMITTEEGENOMICSSTEERING COMMITTEEDS STEERINGCOMMITTEED2B DIRECTORPFCC DIRECTORBIDC DIRECTORGENOMICS DIRECTORDS DIRECTOR

COLABS AT PARNASSUSD2B OrgChartD2B: CENTRAL LABSD2B STEERING COMMITTEED2B DIRECTORTISSUE PROCESSING LABORGANOIDS LABMichelle OghenekevweFranz Villaroel, PhDGabi ReederClinician/Scientist TBDKaren TolentinoTaymour Hammoudi, MD100/20 TechnicianOrganoid-Specific Embed #1Arjun Rao, PhDJasmine SjarifClinician/Scientist TBDClinician/Scientist TBDEvans ShaoAlexis Combes, PhDJessica TsuiEmbedded Scientist100/20 TechnicianKevin Barry, PhDJoy HsuAmar Patel, MDArun BurraImaging-Specific Embed #1Imaging-Specific Embed #2Data Science-Specific EmbedFlow-Specific EmbedEmbedded ScientistEmbedded ClinicianEmbeddedResearchers100/20 Technician100/20 Technician100/20 Technician100/20 Technician100/20 TechnicianTechniciansOrganoids LeadOrganoid-Specific Embed #2EmbeddedResearchersTechnician TBD100/20 TechnicianTechnician TBD100/20 TechnicianTechniciansEXPANSION PROJECTSClinician/Scientist TBDTechnician TBDClinician/Scientist TBDTechnician TBDMouse-Specific EmbedMouse TechnicianEmbedded Scientist100/20 TechnicianClinician/Scientist TBDTechnician TBDClinician/Scientist TBDTechnician TBDClinician/Scientist TBDTechnician TBDEmbedded ScientistEmbedded ScientistEmbedded ScientistEmbeddedResearchers100/20 Technician100/20 Technician100/20 TechnicianTechnicians

COLABS AT PARNASSUSSpace Programming (preliminary)

COLABS AT PARNASSUSDesign Considerations

COLABS AT PARNASSUSSpace Options ConsideredAdjacentStackedSeparated

COLABS AT PARNASSUSCoLabs and the Future of ParnassusThe CoLabs project is important both as a resource and as a symbolMany are deeply skeptical that Parnassus is the best place to do science and acutely awareof the lack of parity with Mission BayCoLabs can help by: Making Parnassus a better, more exciting place to do research Providing a highly visible early example of how UCSF is reinvesting in ParnassusThe success of the CoLabs will require a real commitmentThere are competing demands for space, funds, and attentionFinding a suitable CoLabs site will be hardDetailed CoLabs planning must continue over the coming monthsAn ongoing investment will be required

COLABS AT PARNASSUSSummaryKey principles Be “big and bold” Start now, maintain a sense of urgency, communicate clearly Continue to engage the faculty since many want to help solve problemsand identify opportunities Make the CoLabs a transformational resource for ParnassusMajor recommendations Focus on site selection since this is currently the rate-limiting step We strongly recommend a centrally located, contiguous space ( 20,000sq. ft. or two tower floors) Develop a system for working with displaced groups to find goodrelocation solutions for them Funds will be required for ongoing CoLabs operations as well asCoLabs construction (including relocation) Many CoLabs activities should begin before the new space iscompleted

COLABS AT PARNASSUSCRL Task Force MembersDisease-to-Biology (D2B)Saurabh AsthanaVincent Chan (lead)Hugh Cotter, Oculus ArchitectsDiane KayMax Krummel (lead)Tippi MackenziePatti MitchellJeff MulishJeroen RooseElizabeth SinclairMatt SpitzerScott VandenbergBiological Imaging Development Center (BIDC)Hugh Cotter, OculusDiane KayMax KrummelDiana LairdDelaine LarsenMark LooneyPatti MitchellMatt SpitzerVal WeaverTorsten WittmenKatherine Yang (lead)Flow CytometryHugh Cotter, OculusDiane KayMax KrummelMike LeeCliff LowellPatti MitchellMatt Spitzer (lead)Qizhi TangTransgenicNadav AhituvHugh Cotter, OculusDiane KayAveril MaAlex MarsonMike McManus (lead)Patti MitchellElizabeth SinclairPhysical EnvironmentEric Chow (lead)Hugh Cotter, OculusDiane KayPatti MitchellElizabeth SinclairMatt SpitzerGenomicsNadav Ahituv (lead)Andrea BarczakEric ChowHugh Cotter, OculusLindsey CriswellDavid ErleChun (Jimmie) YeDiane KayAlberto MarquezAlex Marson (lead)Michael McManusPatti MitchellYin ShenElizabeth SinclairRyan WagnerPui Yan KwokData Sciences/Data Library (Bioinformatics)Hugh Cotter, OculusLindsey Criswell (lead)Walter EckalbarDiane KayPatti MitchellElizabeth SinclairMatt SpitzerChun (Jimmie) Ye (lead)

COLABS AT PARNASSUSCurrent locations of related facilities (partial)Disease to Biology/Sample ProcessingHSE 3 multiple rooms (Immunoprofiler)MSB 1234 (CTSI Clinical Specimen Processing Lab)Fong, Spitzer, Ye labs at PHZSFG Building 100 (Core Immunology Lab)Flow CytometryMSB 8 (854a/b, 854, 860)MSB 14 (1456)HSE 3 (301D, 302E)HSW 5 (542)HSW 12 (1209)ImagingMSB 11 (1105, 1109/S1109A, 1114, 1121, 1123)HSW 5 (536, 539)MB Genentech Hall (Nikon Imaging Center)Data Sciences/Data LibraryHSE 304Ye lab at PHMB Rock Hall (Functional Genomics Core Bioinformatics)Functional Genomics (including Transgenic Animals)HSW 9 (IHG) and HSW 10 (Diabetes Center/PCAT)Marson, McManus, and Ye labs at PHMB Genentech Hall (Center for Advanced Technologies, Cell & Genome EngineeringCore)MB Rock Hall (Functional Genomics Core)Gladstone (Transgenic Core)Ahituv and Erle labs at MB

COLABS AT PARNASSUSPreliminary Space ProgramGroupDisease to Biology - D2BTier 1 (Immuno/ Bios/ Organoids)Tier 2- CILTier 3- CTSI- Specimen CollectionPFCC Flow CytometryBIDCData Sciences/Data LibraryGenomicsGeneral Admin/Shared SupportShared Lab SupportSub-totalCirculation @ 35%PermStaffPriv.OfficeSharedOffice# 621615413610 Allows for private offices for ImmunoX/ CRL director, RRP director, shared officefor Strategic Alliance, D2B and Bios managers (total approx. 330 GSF); sharedspaces such as Huddle rooms (6); small Conference (2); Large Conf. (1),Seminar/ Training room; Kitchen/ Break; IDF's; Recycling, Electrical Rms.450 Shared functions such as gas bottle storage, shared fume hoods, chemicalstorage rooms.142604991 May vary from 15% to 35% in lab suites, but calculated at 35% at this time dueto design aesthetic and desire to have open spaces which may increaserequired SF for various program elements and access to them.19251ESTIMATEDTOTAL GSFNotes1. This program has been developed based on meetings/calls with each of the individual groups and meetings/calls with full sub-committee members.2. General Admin / Shared Support includes (3) Management Offices (Private offices for CRL Lab Manager, RRP Manager and shared office for Strategic Alliance, D2B and BIOS); (6) Focus/HuddleRooms; (2) Small Conference Rooms; (1) Large Seminar Room; (1/2) Break Room; (2) IDF; (2) Electrical Rooms; (2) Emergency Supply Rooms3. Shared Lab Support includes shared (2) Gas Bottle Storage; (2) Chemical Storage Rooms; (2) Fume Hoods.4. Hoteling stations not added at this stage; multiple "embedded researcher" stations provided.5. BSL 2* Tissue Culture may not be provided.6. Wet Lab stations are wet lab knee holes and do not include desks adjacent. Some shared desks will be added.7. All information here should be considered as preliminary and should be fully verified.

COLABS AT PARNASSUSAnnual operational support request (first draft)CoLabs Directors Support 180,000Technology Development Projects70,000General Lab Maintenance50,000Operational SupportTotal Annual cost100,000 400,000Courtesy of Elizabeth Sinclair

Nikon Imaging Center in Genentech Hall 191 PIs, 15% at Parnassus Center for Advanced Technology in Genentech Hall 150 PIs, 15% at Parnassus Transgenic Core at Gladstone 35 UCSF PIs, 50% at Parnassus Functional Genomics Co

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