The University of California: irvine Regional Human Embryonic Stem Cell Shared Research Laboratory and Stem Cell Techniques Course
$3 924 479
Statement of Benefit to California:
SHARED LABORATORY SYNOPSIS OF PROPOSAL: This proposal from Dr. Donovan and co-workers at UC-Irvine describes a comprehensive Shared Research Laboratory (SRL) and Stem Cell Techniques Course. The SRL has already been established through donor funds, and a techniques course has been in place for over 18 months. This proposal requests a significant expansion of these activities, including additional space for training, equipment, a small vivarium for animals associated with these studies, and othe related items. The facility already serves many scientists, so the need for expansion is high. Furthermore, the quality and diversity of research associated with the facility is high, particularly in the area of neural regeneration. QUALITY AND IMPACT OF THE SCIENCE: The facility will primarily serve human embryonic stem cell (hESC) research and the leadership (Drs. Donovan, Keirstead, and Lock) has long experience with stem cells. Currently, most of the lines used by these investigators are federally approved but there will be an effort to derive new lines. Thirty investigators are listed as users with 6 CIRM SEED grants approved for award. These investigators are generally well-recognized in their research areas, and have excellent track-records of funding as well as publications, indicating they are highly qualified investigators. The range of research is extensive from basic biology of the hESCs, to cellular models of disease with derivation of novel lines targeting muscular dystrophy, Alzheimer disease, Parkinson’s disease, to clinical trials for treatment of spinal cord injuries and macular degeneration and development of research tools. Several of the suggested pilot studies are said to need federal free environment but the rationale is not very clear. Other than the derivation of new lines, it is unclear why federally approved hESCs are not feasible for use in these studies. Overall there should be important findings both in basic stem cell biology and in therapeutic uses of hESCs. The proposal is responsive to the RFA as it will primarily be used for hESC work. APPROPRIATENESS OF SPACE AND EQUIPMENT TO SCOPE OF PLAN: UCI already has space set aside that was renovated and equipped free of NIH-funds, due to a large donor infusion of funds. The current proposal seeks a substantial increase in space and support facilities (such as a vivarium and a flow cytometry facility), that will make research within the shared labs fully independent and functional. If established as described, this will be one of the largest and most extensive facilities of the type - but this is not inappropriately large. The facility will serve UCI, and possibly investigators at UC-Riverside, and already has generated a large amount of interest through the ongoing techniques course and existing shared lab. The space and equipment is very appropriate. All of the equipment they request is important for hESC work. The special emphasis that this group is putting on developing a facility for small animal models (hESC transplantation) is particularly laudable. The requested vivarium space and associated equipment (such as small animal imaging) will greatly enhance what this SRL has to offer, and is a particular strength. The personnel described for the lab are appropriate. The associate director, Leslie Locke, is highly qualified and has been working with Dr. Donovan for several years. They will have a senior lab manager, and 4 technicians working in the facility, that make up a total of about 2 FTEs. There are a couple of discrepancies in the application that were noted: on p12 it is stated that there is no adequate microscope for analyzing cell populations (thus justifying a need for a microscope with axioimager camera), but both a 2 photon confocal microscope and 3 inverted scopes with DIC and epifluorescence are listed as currently present in the facility. Similarly on p8 it is stated that the current SRL lacks a vivarium but on p7 it is stated that it has a 2000 ft vivarium for which they seek minor renovation. QUALITY OF MANAGEMENT PLAN: The quality of the management plan is excellent, according to one reviewer. There is a clear institutional commitment for an SRL as space has already been allocated, and funds expended to recruit Dr. Donovan and team, as well as to establish the SRL and the current techniques course. Drs. Donovan and Locke are exceptionally well-qualified to establish and run this facility as both have been working with hESCs for several years. These investigators have exceptionally high qualifications for this program. There are a number of investigators at UCI who will have access to the facility, as well as those at UC-Riverside. Access to the facility is to be first come, first served with the requirement of users having a proportion of time and support from non-federal funding, with IRB and SCRO approvals, and an appointment at an eligible California institution. The oversight committee will consist of the co-directors, the director of the stem cell course, the facility manager, 4 users including postdoctoral and graduate students and 4 outside faculty as unbiased external advisors; a total of 14 is perhaps a bit unwieldy. The Shared Facility Oversight Committee will provide input and advice on day-to-day activities of the Shared Facility with monthly meetings that are to be held by video conference. It is a bit complicated since two of the advisors (Carson and Talbot) are also listed as PIs from neighboring institutions who will use the facility. Funds have been set aside for maintenance of the lab and equipment. All supplies are to be purchased through the SRL; this is to keep all federal funding out of the facility but it creates more paperwork. DISCUSSION: This PD is a well-known stem cell biologist with tremendous hESC experience and obvious qualifications to lead such an enterprise. In the 18 months since he joined this institution, he has already started a shared lab and courses in stem cell research. He now describes a plan for significant expansion of training and research space. The proposal includes a small vivarium for animal studies outside of the federal guidelines. The location, number of investigators, and potential for translational research is very high. Although the quality of the science in the proposal is not as strong or well-described as in other applications this institution already has a CIRM training grant and 6 approved SEED grants so there is a community of hESC researchers who has a demonstrated commitment to the field. There is also a translational focus at this institution that could make a major contribution. The applicants have requested a lab manager, and they have Dr. Locke to help with supervision. The management plan is excellent, with people from four outside institutions, which is unique. There is a clear determination to open this facility up to extra-institutional investigators and there is a good plan to implement this. TECHNIQUES COURSE QUALITY OF THE PROPOSED TECHNIQUES COURSE: The institution is already offering a hESC techniques course, which was first given to 24 students in Sept 2006 as a 5-day course. Other sessions are planned in March and May 2007 (each for only 8 students). The curriculum of this initial offering included multiple methods to culture and differentiate cells, and the basics of freezing and thawing of cells using NIH approved hESCs. Not mentioned is training in the problems of genetic instability of hESCs, and how to monitor for this. The students receive both lectures as well as hands-on training and course materials. Not mentioned is a mechanism to follow-up on the students to determine the quality of the teaching to improve the course. The proposal is to expand this to a 2 week course to include more translational techniques: to genetically manipulate hESCs, to transplant them into animal models, to retrieve the cells for histological analyses and imaging techniques of confocal microscopy and live animal imaging. These techniques would enhance the course a great deal, however they might consider offering both a short and long course – as investigators may not always have the desire nor time to attend a 2-week long course. The course will be taught by highly qualified instructors on a quarterly basis and would like to have 16 students per class. The Course directors (Donovan and Lock) have the experience and expertise necessary to direct the course and are drawing from other PIs and trainees for instructors. Plans to advertise and promote the course were not mentioned. The benefit to stem cell researchers is clear, as these are all techniques that are of great importance to stem cell research, and the realization of therapies from these cells. Ethical issues, including use of the IRB and SCRO will be discussed in the course. QUALIFICATIONS OF THE INSTITUTION: UCI is very well qualified to give the course and to provide a shared facility for surrounding institutions. For example, they have a letter from the Vice-Chancellor of Research from UC Riverside indicating great interest in participating in the program. The UCI Stem Cell Center has already offered a hESC techniques course and has a waiting list for the current ones. They have also been offering one on spinal cord injury repair demonstrating a history of such service. The clear commitment UCI has made to the SRL and the fact they are already supporting a techniques course is evidence of strong institutional commitment. There is no formalized follow-up support for the alumni of the courses but the informal network of getting to know the experts. There is also no plan to track students to determine benefits/success of the program. The shared facility would be available for projects that could not be completed in the student’s laboratory at their home institution. One reviewer felt that the proposed tuition of $1500 should be dropped since the proposed course budget will already cover salaries for technicians (at 20-30%), an administrative assistant (25%), 3 of the faculty (at 3-20%), equipment maintenance and about $80,000/year in supplies. The proposed tuition is meant to cover “honoraria, breakfast and lunch for students and supplies not covered in this budget”. DISCUSSION: The Program Director has already been giving a hESC techniques course and is highly qualified as are the other instructors. This current UCI course covers the basics of handling hESCs with lectures, training and hands-on lab work. They have a reasonable track record with the current course and now propose to move into teaching translational techniques, which makes the application very strong. The course will be expanded to include training in the genetic modification of hESCs and in the generation of mouse models - elements which the reviewers find very valuable. The plan for the course does not address a follow up mechanism with the students in the course which the reviewers believe is an important aspect. Overall the course is given by a well-qualified institution with a history of offering courses of this nature. Enthusiasm was somewhat diminished because the proposed course didn’t involve as many outside people as they could have. One reviewer felt that the proposed charges for tuition and other costs such as food seems high. Another reviewer with 10 years of experience teaching similar courses disagrees, noting that the funding requested isn’t really sufficient as a course of this sort is both labor intensive and supply intensive – thus thinks that charging of tuition is justifiable. The reviewer pointed out that offering the course four times a year requires a large commitment of time from mainly internal personnel. This reviewer is impressed with the experience in teaching at UCI and their ability to lay out what they need; this puts them way ahead of other applicants. The commitment to providing the course 4 times per year is quite significant, and the course represents an impressive display of what can and should be done. The current course is a 5 day course that will be expanded to 10 days. The original course had 24 students per class – a rather unmanageable number for a hESC techniques course so it will now be changed to a course for up to 16 students and offered four times a year. Due to research demands on the current hESC shared space, only 8 students/course can currently be accommodated but with the additional SRL space from this CIRM SRL application, the applicants would anticipate training 16 students /session. PROGRAMMATIC REVIEW: A motion was made to recommend this Techniques Course application for funding and the motion passed.