Funding opportunities

The Childrens Hospital of Los Angeles hESC Facility

Funding Type: 
Shared Labs
Grant Number: 
CL1-00507-1.2
Principle Investigator: 
Funds requested: 
$3 320 574
Funding Recommendations: 
Recommended
Grant approved: 
Yes
Public Abstract: 
Statement of Benefit to California: 
Review Summary: 
SHARED LABORATORY SYNOPSIS OF PROPOSAL: This application is to establish a human embryonic stem cell (hESC) lab at CHLA. They propose a 2500 asf (3000 gross) hESC lab that will be shared by multiple investigators. The laboratory will consist of 4 cell culture labs (1 core lab and 3 for general use) plus qPCR, standard PCR, fluorescence microscopy and cryopreservation. The lab will be located in recently vacated space in the Smith Research Tower, which is within walking distance of the labs in CHLA. An appropriate oversight committee is in place. QUALITY AND IMPACT OF THE SCIENCE: The program director is a well-known and respected bone marrow/cord blood stem cell scientist. The facility would serve about a dozen or so investigators at the host institution and some more in surrounding institutions. The proposed users include 19 investigators mostly from CHLA, but also including USC, UCLA, and City of Hope. The institution is clearly investing in embryonic stem cell research and this facility would add to that investment. Although a core laboratory was previously established at CHLA in 2005 with institutional funding, they lack a cohesive space that can be centrally managed, and which can be used for nonfederally approved hESC lines. A training course funded previously has educated 40 scientists from 5 research institutions in Southern California. CHLA also has a CIRM training grant, and at the time of grant submission, they were training 12 CIRM scholars. A broad range of scientific questions are being addressed by the investigators. The work proposed with hESCs is appropriate for the designed facilities. Research of investigators include hematopoietic cell differentiation, self-renewal regulation, viral vectors, pancreatic cell differentiation, and cancer. Proposed investigators also have interests in lung differentiation, signaling, gene expression, immunology, retinal cell differentiation, and GI tract tissue regeneration. Thus, the proposed research focuses on a nice balance of basic and translational studies, with some very unique interests resulting from the pediatric disease theme. There are 4 labs that already work on hESCs including, those of Drs. Crooks, Lutzko, Kohn and Lawlor. In addition, many well established and highly productive CHLA investigators would like to start research using hESCs once the hESC facility is established and they have received funding for the work. The proposed faculty have very good to excellent track records with several already involved in productive hESC research. These projects have either been approved for CIRM SEED funding (Lawlor) or are in the process of being reviewed for CIRM Comprehensive Research Grant funding. Overall, the previous track record of the investigators and the unique pediatric focus are strengths of this proposal. An added strength is the success that CHLA has had in translating cutting edge science in the area of cell and gene therapy. APPROPRIATENESS OF SPACE AND EQUIPMENT TO SCOPE OF PLAN: The facility proposed includes renovation of 3000 square feet of currently vacant space to develop 4 tissue culture suites, four shared equipment rooms, storage and office space. The facility has been designed for up to 12 researchers to be able to work simultaneously. The size of the space is appropriate for the activities planned. These rooms will contain relatively standard equipment. Funds are being requested for PCR machines, fluorescence scopes, etc, all of which are appropriate for the studies proposed, and would be needed for work on nonfederally approved hESC lines even if similar equipment purchased with NIH funds is available in the labs of individual investigators. In addition, an Image Stream Cell Analyzer is proposed to be purchased with some funding from the institution. The Smith Tower at CHLA also contains a variety of other core services. Space renovation will be overseen by an experienced administrator. Since there is already a core in place, much of the experience and management will be easily transferred to this new facility. The proposed plan is highly feasible as it expands on existing expertise. They are certainly not requesting too much, but the space requested should be adequate for now. QUALITY OF MANAGEMENT PLAN: Dr. Crooks has presented an excellent plan for administration of the lab with appropriate oversight. She has put together a well-trained and experienced staff including 100% of a Lab Manager, who has over a decade of experience in cell culture and molecular biology and over 4 years of experience in culturing and QA/QC of hESCs. She has been the lead technologist at the CHLA hESC core lab since its inception in 2005. The budget requested is adequate and appropriate. For the key personnel, 5% effort is listed for Dr. Crooks, 10% for Dr. Lutzko, as well as 100% of a lab manager, 50% of a technician to work in the hESC culture facility and 30% of a technician who will oversee the flow cytometry core. In addition, funds are requested for supplies as well as operations and maintenance. Access to the CIRM sponsored core will be limited and will provide equipment, assistance in technical development, and access to investigators with experience in hESC culture. An oversight committee will review applications to the facility and provide prioritization based in part on CIRM funding. Mandatory requirements for entry are enunciated in the application and include all regulatory approvals and specific training. Prioritization policies have been established and are clearly stated. The overall program includes access to space, training, development of high quality hESC stocks and development and sharing of protocols. The oversight committee includes Crooks, Lutzko, Kohn, Driscoll, Epstien, and Lew. There is sufficient expertise on this committee to ensure adequate oversight, although it is noteworthy that all members are faculty at CHLA. There is no mention of how often meetings are to take place. DISCUSSION: These are superb investigators doing good work. The other investigators are well-established, but not yet working with hESCs. This can be considered both a strength and a weakness. There is a nice mix of basic and translational work, and CHLA is a leader in gene therapy translational work. The size of the lab, designed for up to 12 simultaneous users, is considered appropriate. The laboratory manager is very well-qualified, a lead technologist in hESCs. There is a good use of funds for personnel. There are 12 CIRM scholars already at the institute, and a course is up and running. There is a good prioritization plan for the lab that will give priority to CIRM-funded investigators, and users will apply to the oversight committee to get work approvals. There is a pediatric disease base that is interesting and also a strength. This was a terrific application from a group with a distinct focus.
Conflicts: 

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