We propose the creation of "Regenerative Sciences Stem Cell Biology Open Research Center." The mission of this facility will be to create a value-added shared research facility that will provide a unique environment to conduct research on hESCs, and create and maintain hESCs. Regardless of whether RSI wins funds for a Stem Cell Techniques Course, our facility will not only offer shared research space for hESC research, but will provide training and courses in how to conduct such research for small groups, and make that training publicly available through multimedia presentations on the web and CD/DVD. Furthermore, our shared research facility will take advantage of our unique research environment in which people from the high school to faculty levels are brought together to collaborate on cutting-edge research, where the conventional hierarchical management structure is eschewed in favor of a collegial approach. We will actively encourage people with possible research interest in stem cell biology to propose exciting high risk/reward work. We will then select those meritorious proposals and workers who would best benefit from our unique environment. Should another stem cell research center be funded in our vicinity we will work with them to add value to their services by working with groups of workers who might not otherwise have the opportunity to conduct original work in human stem cell biology. The facility will be managed by a committee consisting of staff from RSI, as well as representatives from the local universities and colleges. Decisions will be made by close adherence to the collegial principles already described. We will actively solicit research proposals from neighboring educational institutions at the faculty, postdoctoral, and graduate school levels. In addition, we will expand our existing fellows/interns program by selecting a group of fellows and interns from local colleges, universities and high schools to be trained in human stem cell biology and encouraged to propose and conduct original research in collaboration with the more senior researchers.
Statement of Benefit to California:
We propose the creation of "Regenerative Sciences Stem Cell Biology Open Research Center." The mission of this facility will be to create a value-added shared research facility that will provide a unique environment to conduct research on hESCs, and create and maintain hESCs. The center will not only act as a conventional shared facility for stem cell research, but will bring all the benefits of open biological research. The center will be open to all interested faculty, will promote education of young researchers and will pursue high risk, high reward scientific research. CA research infrastructure will benefit.
SHARED LABORATORY SYNOPSIS OF PROPOSAL: Dr. Andrew Mendelsohn proposes the creation of the “Regenerative Sciences Stem Cell Biology Open Research Center,” to be associated with the Regenerative Sciences Institute (RSI). They will offer shared research space to conduct research on human embryonic stem cells (hESC), including the creation and maintenance of hESCs. The Center is envisioned as an incubator for diverse invitees - from high school students to faculty investigators - who will learn the techniques for hESC research in this unique research environment. The Center will emphasize a collegial approach and encourage high risk/high reward investigation. It will be managed by a committee of staff from the RSI, Palo Alto Institute of Molecular Medicine, and two ad hoc representatives from local universities and colleges. QUALITY AND IMPACT OF THE SCIENCE: This is a proposal to create an “open, shared human embryonic research and education center”. The focus is to develop a facility to maintain hESCs, a structure to incubate seed projects from a variety of scientists and thus become a training center for a diverse group of researchers entering the field. The proposal is to integrate a volunteer undergraduate internship program with new programs for graduate students and post-doctoral fellows. The range and quality of hESC research cannot be judged from the application, as no pilot projects are described and no specific scientific questions are defined. The Director of the Center, Dr. Mendelsohn, has twenty-five years of experience in molecular and cellular biology in research and as a consultant to industry. He proposes to devote 30% effort to this undertaking. He received a BA degree in 1981 from the University of Pennsylvania and the PhD from Brown University in Molecular Biology, Cell Biology, and Biochemistry. He was a post-doctoral fellow with Roger Brent at Massachusetts General/Harvard Medical School from 1991-1997. He had subsequent research positions at the Molecular Sciences Institute in Berkeley, CA and he is an Assistant Professor at RSI. He has served as an Instructor at the University of Berkeley, CA and Instructor at the RSI. While he is author of nine publications, including first author publications in Proc Natl Acad Sci USA and Nature Biotechnology, his biosketch shows no papers on ES cells and no external funding. The only description of specific projects in the proposal is a brief allusion to preliminary unpublished work by Dr. Mendelsohn who is studying gene expression patterns and regulation in differentiated cells, such as fibroblasts and neutrophils with hESC regulators, such as nanog. This does not permit assessment of the approaches and goals. He does describe a special emphasis on directing somatic cells toward pluripotency, but no further details are provided. Other key personnel listed likewise appear to have no published experience in ES cells or indeed in any stem cell field. Dr. Wright is Associate Research Director and Professor at the RSI. Her last listed peer-reviewed paper dates to 2003. The laboratory manager, Jennifer Lei received a BA degree from the University of California, Berkeley in Molecular Cell Biology in 2007 and she has taught as an instructor at RSI. Dr. James Larrick received MD and PhD degrees from Duke University and he is currently the scientific director of the Palo Alto Institute of Molecular Medicine Research in Mountain View, CA. Dr. Larrick will serve on the Oversight Committee. He is author of more than two hundred peer-reviewed publications in biology and pharmacology, but his last peer-reviewed paper dates to 2003. No funding is listed for either Dr. Wright or Dr. Larrick, and no other faculty are listed. Given the lack of any published hESC experience, or indeed experience in stem cells of any kind, the potential for this program to generate high impact discoveries does not appear to be high. APPROPRIATENESS OF SPACE AND EQUIPMENT TO SCOPE OF PLAN: It is difficult to evaluate the appropriateness of the request based on the information provided. The application plans to expand from 6 to 15 the number of undergraduates from Stanford and Berkeley who will be accommodated in six-month internships; a similar program is planned for graduate students and post-docs. Such interns will be integrated into research teams that will include at least one faculty member. However, it is unclear how many teams will operate at any given time, the size of the teams, or how the team members will be selected and assembled. The additional 1400 square feet that are proposed for renovation might reasonably accommodate two or more small teams. Plans for the renovations will be overseen by the lab manager. The applicant states that 1400 square feet of space within existing RSI facilities will be allocated to development of the new center, yet these “existing facilities” are nowhere described. Without some notion of the existing infrastructure for research at RSI, the space and equipment request cannot be assessed. The proposal is to use funding to purchase major equipment that will be utilized to culture and maintain hESC. The equipment mentioned is standard tissue culture equipment; however, the supply budget listed is for $80,000/year with no justification and there is no specific budget for equipment purchases. This budget for supplies appears excessive, especially considering the requested supply budget for the course. It is possible that the requested funding is for equipment rather than supplies, but in the absence of any justification, this is difficult to determine. QUALITY OF MANAGEMENT PLAN: Collectively the management team seems poorly configured. The management plan is similarly vague and not conducive to the ongoing development and support of rigorous science. The facility will be managed “by a committee” consisting of the staff from RSI, the Palo Alto Institute of Molecular Medicine, and two ad hoc representatives from the local universities and colleges who will be selected on a rotating basis (how is not defined). The Oversight Committee will include Dr. Mendelsohn, Dr. Larrick, and Ms. Lei, a recent college graduate with no advanced degree. This individual is also named as the Director of Research Administration on the face sheet of the grant application. Dr. Mendelsohn played a key role in setting up the Molecular Sciences Institute in Berkeley under Dr. Sydney Brenner, and as co-founder of RSI he has established its infrastructure, procured space, and raised funds. There is no plan to review the success of this program, nor are the goals of this research described beyond that of an open, shared facility. The RSI states a clear commitment to sharing the space with investigators from other institutions. Operationally, the plan is for the lab manager (Ms. Lei, 45% effort) to delegate equipment usage with sign-up sheets and prior reservations. In special cases, equipment will be assigned on a needs basis. A research assistant is listed at 100% effort, but not discussed. The RSI oversight committee will vote on allowing visiting faculty and students to participate in the program. No parameters for this decision are provided, but there is an anticipation of up to 10 visiting faculty at one time. Laboratory operations will be supervised by the laboratory manager and guidelines are included, which are relatively vague, but state that the projects will be reviewed and approved by the oversight committee. DISCUSSION: There was no further discussion following reviewers’ comments. TECHNIQUES COURSE QUALITY OF THE PROPOSED TECHNIQUES COURSE: A stem cell techniques course will be taught by staff from RSI. The quality of the proposed course seems very low. The course will consist of basic training in cell culture, molecular and cell biology relevant to hESC followed by an independent research project. The course will be offered quarterly and be taught in the context of “collegial educational philosophy”. It will be offered quarterly to ten visiting faculty members (in conjunction with the Open Research Center), to existing fellows/interns, and to others from local universities, colleges, and high schools. How will one curriculum accommodate such a wide range of student backgrounds? The course will be distributed via multimedia presentations on the web and by CD/DVD. It is unclear how the $80,000 annual supplies budget will be utilized. Plans for advertising the course are not described, and no details regarding assessment of the success in training are provided. QUALIFICATIONS OF THE INSTITUTION: Given the lack of many of the specifics needed in the grant application and the paucity of faculty (particularly with experience in hESC and adult stem cells), the qualification of the institution to organize and implement this course appears low. Dr. Mendelsohn, who will co-coordinate the course with Ms. Lei, has experience in the education of high school students and undergraduates and was an Instructor at University of California at Berkeley in 2005. Their respective 30% efforts for this course appear to be in addition to their efforts in supporting the Research Center. Other positions are TBD. The RSI currently has an existing undergraduate intern program enrolling students from Stanford and Berkeley and the application states that RSI has implemented a version of the ‘open biology’ approach in the Mendelsohn laboratory with 5 high school interns and 6 undergraduates. However, there is nothing in the proposal which speaks to the quality of these students, or the success of the course. No detail of course content is available and no track record of previous training is available. Finally, there are few details with respect to how such a course will be advertised DISCUSSION: There was no further discussion following reviewers' comments.