Funding opportunities

Collaborative Laboratory for Human Embryonic Stem Cell Research at Sanford-Burnham Medical Research Institute

Funding Type: 
Shared Labs
Grant Number: 
CL1-00511-1.1
Principle Investigator: 
Funds requested: 
$4 566 881
Funding Recommendations: 
Recommended
Grant approved: 
Yes
Public Abstract: 
Statement of Benefit to California: 
Review Summary: 
SHARED LABORATORY SYNOPSIS OF PROPOSAL: This proposal is to expand a current privately funded shared facility for non-federally funded human embryonic stem cells (hESCs). The Burnham Institute for Medical Research (BIMR) has had such a facility operated by experienced stem cell researchers since 2004, and it currently provides a crowded space for 40 principal investigators (PIs), with researchers approved for both CIRM awards and other non-federal funding. Additionally, two stem cell technique courses are proposed; one is a short basic course and the other a longer advanced one. QUALITY AND IMPACT OF THE SCIENCE: This facility and course are well-planned administratively and the overall impact should be great. The PIs of this facility are varied in their research interests and outstanding in their stem cell biology research with both basic stem cell biology and therapeutic uses. The application includes internationally recognized experts in fields that utilize stem cells, and include original and important scientific questions. More than 80 publications have resulted from the research of PIs at the institution. This application carefully delineated the non-NIH funding already in place for hESC studies and described well the main areas of research. This proposal is designed to fund an open laboratory that will be available to a consortium of scientists working on hESCs in the major research institutions in San Diego. As such, the range of research being carried out in San Diego is remarkable, as identified in twelve different areas of research. These areas cover almost the entire gamut of research on ESCs. Current research at the BIMR relating to hESCs includes, 1) improved maintenance of hESCs 2) generating new hESC lines, 3) studying the molecular basis of pluripotency and differentiation, 4) understanding regulation of hESC gene expression, 5) creating a database of transcriptional profiles for hESCs and other stem cells, 6) developing methods to direct hESC in specific lineages, 7) using high throughput screening technology to identify small molecules that direct differentiation, 8) using high resolution quantitative microscopy to study migration of hESC derivatives, 9) modulating self renewal in pluripotency through specific signal transduction pathways, 10) developing hESC-derived cellular models of human disease, 11) testing the therapeutic potential of hESC in animal models, and 12) investigating the relationship of stem cells in neoplasia. The non-federally funded lines are considered preferable by this group for their studies due to their more stable genotype and phenotypes, more amenable culturing in defined conditions and greater reproducibility. Additionally, as part of the San Diego Consortium for Regenerative Medicine, BIMR will invest in derivation and characterization of new hESC lines and maintain banks of these cells and of donated embryos for further derivations. The other institutions have focused on technologies for the benefit of all; these include automated methods of gene targeting, engineering methods for expansion and controlled differentiation, development of viral vectors and libraries for gene transduction, and cell-based screens of chemical and genomic libraries. Thus the synergy, strength of research, and expectations for this Shared research Laboratory are outstanding. The investigators at the BIMR have outgrown their current NIH-free space set aside for research on non-federally approved cell lines and they wish to develop an open-plan 4000 sq. ft. lab with modular design. They will provide specialized research support by sharing expertise in the development of new hESC lines. The program director, Dr. Jeanne Loring, is an expert in characterizing stem cells. She will oversee all aspects of the program and be supported by a small technical staff, including the Laboratory Manager, Mr. Chris Stubban. The BIMR has already succeeded in gaining approval for a number of awards from CIRM as have the other institutions in San Diego, underscoring strengths in stem cell research within the community. This combined scientific power, along with their apparent commitment to share and collaborate, makes it almost certain that they will generate high impact scientific data of the highest quality. APPROPRIATENESS OF SPACE AND EQUIPMENT TO SCOPE OF PLAN: Burnham already has a 1000 sq ft lab dedicated to non-federally approved hESC research, but due to increased interest (from 5 initial to 40 current members) and additional funding, they propose to expand their current facility with a 3000 sq ft main laboratory with three modules, one for the technical staff and the other two for research that will be equipped with hoods, incubators and fluorescent inverted microscope-digital camera set ups. BIMR has other shared facilities for advanced technology that are also available for the most part due to non-NIH funding for their equipment. The need for additional space at the BIMR Stem Cell Center is well-documented in the application, and includes the need to provide for research that is currently unsupportable by NIH. The application describes expansion of the current 1,000 sq ft to 4,000 sq ft, including shared laboratory space and areas for the training courses. The current space is being utilized nearly around the clock. They will utilize a modular design to provide flexibility for continued growth of investigation in this area. Laboratories will be outfitted with equipment required for tissue culture, and will include fluorescent and dissecting microscopes, cryopreservation equipment, a flow cytometer, and other appropriate equipment. They have allocated a significant amount of space and planned the division of the space appropriately. It would have been helpful if they had listed the requested equipment and the respective costs. What they do describe, however, seems appropriate although it would be helpful to know what equipment currently exists in their current “safe-haven” hESC facility. This institution strongly supports the development of a new and larger lab. QUALITY OF MANAGEMENT PLAN: With the benefit of already two years of experience with such a shared facility for non-federal hESC lines, BIMR has been able to develop a reasonable and workable plan for assuring smooth functioning and all necessary compliances. The program director, associate director, and laboratory manager will oversee the Shared Research Laboratory. Both the program director and associate director have great experience in stem cells as well as managing the shared facility. The laboratory manager is experienced and has worked closely with Dr. Loring for the past year. The shared laboratory should accommodate forty full-time member researchers. The oversight committee includes stem cell scientists from neighboring institutions and so will have expertise as well as objectivity. One reviewer commented that the oversight committee of 15 people seems unnecessarily large and unwieldy. Allocations of space are determined by the Oversight Committee, and reviewed quarterly. Despite the pressing space demands, this mechanism appears to be functioning adequately. Access to the Shared Research Laboratory is controlled by keycard, and comes with a requirement for training in equipment and ethics. The technical staff will provide basic supplies, quality controlled reagents, tested methods and well-characterized cell lines as well as training and quality control. Certain items (cell bank and frozen stock) will be restricted to the technical staff for quality control and monitoring. DISCUSSION: Reviewers agree that this is a well-developed proposal to expand an existing facility; this facility started small, but is now crowded with 40 PIs, 8 researchers approved for CIRM SEED awards, a CIRM training grant, and 2 researchers approved for CIRM Comprehensive awards. This facility is operating 24 hrs a day with people working in shifts. The program director, Dr. Loring, has industry experience and a great deal of experience running core facilities and overseeing complicated collaborations. This is a member of the San Diego consortium and is focused mainly on the generation and characterization of new human stem cell lines, and for maintaining a cell bank. This group is all-encompassing with strength in research and synergy. The new laboratory will extend what they already have, adding 3000 sq ft; 3 modules, 1 for technical staff who will do quality controls. Two modules will be for research directly. Burnham has a number of shared facilities, most built with non-NIH funding, so they will be available for non-presidential hESC research. They already have 2 yrs of experience running one of these Shared Research Laboratories. They have a good technical staff including an experienced lab manager, and they have thought through the technical aspects. In sum, this is a very well done application from a very impressive group. Another reviewer agrees with most of the comments, but adds a couple of minor points. Their oversight committee with 15 people is very large and could be cut in half. Dr. Snyder seems over-committed, and Dr. Loring will be major force in the SRL. The proposal is a little slim on technical support and it seems to this reviewer that they will be short-handed. It also strikes the reviewer as odd that Dr. Loring will review all the publications. The third reviewer comments that the need is truly great at this facility, and that there are many funded investigators, including some with funding from the Juvenile Diabetes Research Foundation, who would use the facility. TECHNIQUES COURSE QUALITY OF THE PROPOSED TECHNIQUES COURSE: The proposal describes a Basic Course that will be held seven times in the first two years, and an Advanced Methods Course to be taught in years 2 and 3. The content of the courses is well-described, and will be supported by a comprehensive laboratory manual. The basic course will include all aspects of stem cell research, including ethics; the advanced course will be designed as needed utilizing the expertise of the various members. There will also be a special one-day Public Education Program offered twice a year for non-biologists and will include politicians and journalists. Training draws on the experienced staff from Scripps, Salk, UCSD, and BIMR. Courses will be advertised through the BIMR website, and a variety of other media. The courses will be free of charge to academics, but will charge a reasonable fee of ~$1500 to non-academic participants. The experience of the instructors and the well-defined curriculum are substantial strengths of the courses. One reviewer states they provide a detailed plan for the basic course in the application but not for the more advanced one. The basic course plan seems to cover all the necessary background to allow the students to establish their own ESC cultures. This reviewer considers a three day course possibly to be a bit short. Certainly the advanced course, which is not totally formulated at present, would take longer than three days. The planned frequency of delivery of the courses and their reasons for making those choices could have been explained better. This reviewer states they have only strength in organizing training courses and no apparent weaknesses. QUALIFICATIONS OF THE INSTITUTION: This institute already has demonstrated its ability to give such courses and at present is one of the seven NIH-funded national hESC training sites (10 day courses) and is one of six NIH-funded hESC Exploratory Research Centers. There is some care taken to separate these courses as far as the technical help is concerned but one wonders if the non-federal cell lines are actually needed in the basic CIRM course or not. Their course will draw from the faculty of the San Diego consortium thus adding to the given strength of expertise at the BIMR. Alumni will have access to an online discussion group and a yearly symposium for alumni presentations. One reviewer comments that mechanisms for documenting the effectiveness of the courses are not adequately described. DISCUSSION: There was no further discussion beyond the comments of the reviewers. PROGRAMMATIC REVIEW: A motion was made to recommend this Techniques Course application for funding, and the motion passed.
Conflicts: 

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