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CIRM MAJOR FACILITIES GRANT APPLICATION #FA1-00616-1
Recommendation: Recommended for further consideration as a CIRM Special Program
Element X Score: 70
Element Y Score: N/A
Element Z Score: N/A
Use & Contribution Score: 70
Public Abstract (provided by applicant)
We propose a CIRM Special Program (Research Element X), supporting basic and discovery research that will fund renovation of space to provide for the establishment of a new Center for Stem Cell Biology and Engineering. CIRM funding will allow us to expand our growing basic research on human embryonic stem cells (hESC) by creating a state-of-the-art facility for new faculty, for collaborative work and for core facilities. We will transform antiquated, inadequate laboratory space to allow research that will be free of federal restrictions.
Research in the proposed Center will focus on two areas of basic and discovery stem cell research: Molecular Mechanisms and Bioengineering. First, studies will focus on the fundamental molecular mechanisms of stem cell growth and differentiation, using hESC and stem cells in simpler organisms that are useful models of developmental processes and disease pathobiology. The second goal will be to investigate novel methods for stem cell growth, differentiation, sorting and delivery, using synergistic cell biological, biomaterial, and bioengineering technologies. The long-term goal will be the application of results to the development of stem cell-based therapeutics for human disease.
Renovation of about 10,000 asf of space, most of it adjacent to the CIRM-funded shared hESC lab, is proposed to accommodate the following three program elements:
- Space for new faculty members. Laboratory space will be renovated to provide for two new senior faculty members, for which searches are underway. The first, in the area of molecular mechanisms, will fill an endowed chair and act as director of the new Center. The second, in the area of bioengineering and systems biology, will fill another endowed chair.
- Space for collaborative work. Space free of federal restrictions will be renovated to provide for the expansion of ongoing collaborative work between investigators at our institution and those outside our institution. This will stimulate collaboration and exchange of ideas that would otherwise not be possible.
- Core Facilities. A much needed Flow Cytometry Core will be established within the facility. Additional renovated space will house Center equipment rooms, meeting rooms, and offices. Finally, several vivarium rooms in the same building will be renovated to accommodate stem cell experiments in animal models. These core facilities will be used by researchers at our institution with ongoing stem cell projects.
This CIRM Special Project will provide crucial funding that will greatly stimulate growth of stem cell research. It will facilitate new, interdisciplinary collaborations that would otherwise be impossible due to federal restrictions and lack of suitable space.
Statement of Benefit to California (provided by applicant)
California, like much of the United States, is facing a staggering challenge to its health care system. A perfect storm of soaring medical costs and the aging of the population augers poorly for the economic future of health care as we know it. Increasingly physicians are treating chronic, debilitating, and therefore expensive diseases with organ specific impairments. The demographic wave of the Baby Boomers will accelerate many of these issues. By 2020 they will average 64 years of age. As a result, the percentage of elderly in California is expected to grow from what was 14 percent in 1990 to 22 percent in 2030. Chronic degenerative diseases, which tend to afflict an aging population, represent a proportionally high percentage of individuals in California. Major innovative approaches are now, more than ever, an imperative. Our stem cell program, with its emphasis on enabling technologies, has the potential to make an impact upon many of these conditions.
Degenerative diseases are those diseases caused by the loss or dysfunction of cells. Examples include cardiovascular disease, osteoarthritis, Parkinson’s disease, osteoporosis, diabetes, and macular degeneration. Among these conditions, stem cell work at our institution would leverage a strong existing program in macular degeneration, a condition that is just beginning to be addressed in the stem cell field. Stem cell work for eye disease holds the promise of being an exemplary candidate for cell therapy that could lead the way for the entire field. Targeting clinical conditions that represent “low-hanging fruit” for the field and delivering an early clinical success will clearly benefit the state.
We propose renovation of space to create a Center for Stem Cell Biology and Engineering, where biologists and engineers collaborate on basic and discovery research projects directly relevant to stem cell therapeutics. This highly interactive mix holds a great deal of promise for the opening of stem biology to the bioengineering community, and the development of materials and devices for the stem cell field.
In addition to the medical potential of stem cells and the spear heading of interdisciplinary work, our program will also bring economic benefits to the state. Multiple collaborations with industry have already emerged from our program in a very short time, stimulating growth of the California biotechnology industry.
Review Report
Executive Summary
The applicant institution proposes the renovation of 10,000 square feet of space adjacent to an existing CIRM-funded shared laboratory to support basic and discovery research (Element X) and the establishment of a center for stem cell biology and engineering (a CIRM Special Program). The proposed CIRM funding will expand basic research on human embryonic stem cells (hESC) by creating a state-of-the-art facility free of federal funding restrictions. Research in the proposed center will focus on two areas of basic and discovery stem cell research: molecular mechanisms and bioengineering. Laboratory space will be renovated to provide for two senior faculty to be recruited, and for collaborative work with an eminent hESC expert from out-of-state, who has a 20% appointment at the applicant institution. It will also house a flow cytometry core and several vivarium rooms.
The strengths of this proposal are the part-time recruitment of an eminent scientist who can catalyze hESC research at the applicant institution; the strong involvement of engineering in stem cell biology on campus; and growing activity in ESC biology at the insitution. The weaknesses are the lack of more senior ESC biologists; the fact that the space will be used only for three senior researchers, rather than a more mixed (and thus possibly more vibrant) community; and lack of imaginative core facilities. The applicant institution has an outstanding program in materials science and the possibility exists for creative applications in stem cell biology. However there is, as yet, little evidence for such productive inter-disciplinary collaborations.
Detailed Summary
Element X
Score: 70
SCIENTIFIC PROGRAM: The proposal lists 25 faculty with expertise in the areas of stem cells and retinal disease, molecular mechanisms of hESC differentiation, and bioengineering of stem cell systems. It is noted in the application that all of these investigators will have their main lab space outside of the proposed facility, but will make use of it and are in close proximity to each other and the site of the proposed facility. According to one reviewer, these investigators are all very talented, however their caliber is below that of other top California universities.
The research elements are broken into two areas: molecular mechanisms of stem cell biology and bioengineering applied to stem cell biology. The former will focus on differentiation of hESCs into retinal cells, and hosts a number of researchers with significant experience in the eye and some with experience in hESCs. A second molecular mechanisms focus is on hESC differentiation primarily into neural cells. Most of the investigators in this area are planning or just beginning research in hESC biology; this is a positive in that the facility would help spur such endeavours, but a negative in that only two have a track record in working with hESCs. In the second area of research, bioengineering of stem cell systems, one focus is in biomaterials, supported by the participation of a number of distinguished materials scientists who have an interest, but not much background, in stem cell biology. The second focus is in stem cell sorting. The investigators are again well-regarded in cell sorting but without much experience in hESC biology. The investigators will remain in their existing laboratories, except for the part-time out-of-state scientist, for whom wet space in the facility will be provided.
FORMAL INSTITUTIONAL COLLABORATIONS: In addition to intra-campus collaborations, this proposal lists ongoing collaborations in stem cell research with several academic institutions in California as well as outside the state and with several biotech companies. Several of these collaborations are long-standing and have a proven track record.
The primary institutional collaboration is an agreement among several area universities for sharing stem cell facilities, courses, and materials. This is a strong and helpful agreement. There are many other interactions in place between the proposed facility and institutes within the applicant organization, but no discussion of how these collaborations will be affected by or will themselves affect the proposed facility.
CORE SERVICES: Proposed new core services include a flow cytometry core and vivarium rooms for work related to hESC research. The proposal also includes as “core services” the addition of renovated space to house equipment, meeting rooms, and offices.
The flow cytometry core will centralize scattered equipment already on campus, as well as house new additions. The core will be made available to both the campus as well as collaborators in the region.
Proposed core services are to be integrated with existing cores, including a CIRM-funded Shared Laboratory, a microscopy facility, and a proteomics and genomics core facility. This certainly is one of the clear advantages of this proposal.
PLANS FOR GROWTH: This is a forward-looking plan with the merit of seeking to build upon past successes with the aim of establishing a solid stem cell biology research program. Renovated space will house offices and lab space for two endowed chairs, who are currently being recruited. Other faculty will be hired in related departments/institutes on campus. The building capacity and plans to hire new faculty are in line with the stated goals of this RFA.
DISCUSSION: Overall, the proposal was not well-written, and the reviewers felt that this application lacked excitement. It highlights good basic science in the retina and addresses an important clinical problem, macular degeneration. The institution’s part-time recruitment of an eminent hESC scientist from out-of-state gives them an edge in studying the molecular mechanisms of hESC differentiation, although this scientist will only provide a 20% contribution of time. A discussant cautioned that in his/her experience, 20% appointments do not necessarily translate into one-day-per-week efforts as the percentage implies. The bioengineering plan is also decent, although there is little experience in stem cells and the outcome will not have clear significance to the field. One reviewer was uncertain whether this institution is the best place to develop cell sorting and microfluidics technologies, since there are many good commercial entities with this expertise. There are extensive existing collaborations with other institutions, although no new collaborations were established to support the goals of the facility. The core services have a good track record. The growth plan is ok, but not particularly ambitious. It allows for the recruitment of two investigators in stem cells (not bioengineering).
Use & Contribution
Score: 70
Overall, this proposal fulfills the three criteria listed by CIRM as crucial for the use of the proposed facility and its contributing programs and PIs, including 1) well-integrated elements; 2) well-planned and appropriate planned use of the proposed facility; 3) contribution of the proposed facility to the development of the applicant institution’s stem cell program.
The use of the facility will be primarily by the three faculty housed there and the users of the flow cytometry core. The core will be operated on recharge basis with a steering committee of biologists and engineers. It is very likely that housing the part-time eminent stem cell scientist and the two chairs will lead to a surge of collaborations at the applicant institution. It would have strengthened the proposal to see a more formal plan for how these three people would interact with the nascent stem cell biology program at the applicant institution.
DISCUSSION: One reviewer commented that only 3 faculty would be using the facility, whereas another reviewer expected that use will increase as the institution brings in accomplished stem cell biologists who will encourage collaborations with retinal scientists and engineers. However, there was no real plan.The reviewers ended up having to rely for their evaluation on the investigators the institution is planning on recruiting.
The following Working Group members had a conflict of interest with this application and were therefore recused from participating in review of, discussion of, and voting on the application:
- Feit, Marcy