$3 981 392
Statement of Benefit to California:
SHARED LABORATORY SYNOPSIS OF PROPOSAL: This application proposes to build on an existing core facility at UCSD, established in 2005 with private funding. Demand for this facility has outgrown the current space and funding, hence this proposal. This includes the development of a satellite facility at UCSD’s engineering school to design and test new approaches and technologies for manipulating human embryonic stem cells (hESCs). There are four scientific objectives for this proposed facility. The first is the development of methods for efficient gene modification of hESCs. The second is the improvement of differentiation methods. The third objective is the establishment of culture systems for large-scale expansion of hESCs. The fourth is to design and synthesize novel materials for the growth, differentiation, and characterization and delivery of hESCs. QUALITY AND IMPACT OF THE SCIENCE: This is an outstanding proposal. It addresses critical components of propagating hESCs and developing optimal implementation procedures. According to one reviewer, there is no doubt that genetic engineering will become a key aspect of acquiring the best cell types. Also, large scale culture systems are of pivotal importance for therapeutic implementation. This reviewer is particularly impressed with the proposed inter-disciplinary scientific approach of working with experts in nanotechnology and biomaterials to test novel encapsulation procedures as well as matrix/growth substrate development. This comprises true “cell engineering” and this is what the scientific community needs. The program director, Dr. Willert, is an assistant professor who was hired as an assistant adjunct professor in 2005. The facility will participate in the San Diego Consortium for Regenerative Medicine. According to one reviewer, there is no question that this facility will serve some of the best scientists in the world. The San Diego Consortium alone can boast of being approved for nearly 20 CIRM SEED awards. However, it was not clear to this reviewer how many of the investigators will rely on this particular facility for hESC culture and the extent to which this facility will be crucial for their work. APPROPRIATENESS OF SPACE AND EQUIPMENT TO SCOPE OF PLAN: The institution’s current stem cell core facility located in the School of Medicine consists of 2,211 square feet of lab space. An additional 12,000 square feet has been allocated for active and future faculty recruitments in hESC research. Researchers at UCSD were recently approved for 6 CIRM SEED awards, placing a greater demand on the core facility. The School of Engineering has allocated an additional 3,950 square feet for a satellite facility. This proposal requests funds for the renovation of these two spaces and additional equipment to meet increased demand due to funded and pilot projects. Toward the goal of developing methods for genetic manipulation, particularly homologous recombination of hESCs, funds are requested for the following equipment: a FACS Aria machine, confocal microscope, electrophysiology unit, centrifuges, biosafety cabinets, Amaxa Nucleofector electroporator, and a computer network and server. Additional equipment for the satellite lab and the engineering school includes a live cell imaging and purification system, a Fourier Transform Infrared spectrometer, GPC light scattering detector, microarray spotter, and polymer encapsulator. In general, the reviewers agree that the space and equipment are appropriate to the scope of the plan, although sufficient details were not provided in the application for some of the equipment (e.g. the "polymer encapsulator”). QUALITY OF MANAGEMENT PLAN: Reviewers agree that the management plan is excellent. The proposed scientific direction and staff for this facility are excellent and will draw primarily on the current staff of the core facility, including Dr. Karl Willert as Program Director, who has been in charge of the UCSD core facility since its inception in 2005. One reviewer points out that Dr. Willert is not highly experienced in hESC research or in management of a major facility, being just a few years out of his postdoctoral fellowship, although with industry experience. Oversight for the core facility will be conducted by an inter-departmental steering committee, overseeing the strategy, budget and management of the shared laboratory. UCSD has demonstrated its commitment to hESC research since its establishment of a non-federal core facility in 2005, and has since maintained and characterized several stem cell lines successfully. DISCUSSION: This is an outstanding proposal from a program director who is promising, energetic, and fairly junior. This proposal differs from others in the proposed interdisciplinary studies with engineers who are expert in nanotechnology and biomaterials; this could be key for developing encapsulation technologies which may be important for successful cell transplantation. The proposal for large scale culture systems is also regarded by a reviewer as a very useful component of the shared facility. This Shared Research Laboratory clearly will be useful as core facility and the institution has already put a great deal of effort into developing hESC research. There is no overlap with other institutions in the San Diego consortium. The likelihood of success is good because the management has been running a hESC core since 2005. A reviewer points out that the program director is only 4-5 yrs out of his PhD training and therefore this director does not have the ‘gravitas’ that other facility center heads do; this reviewer would have preferred more a more senior investigator to direct the facility. While another reviewer agrees, s/he points out that this program director is likely to be dedicated to the success of the Shared Research Laboratory whereas more senior scientists are less accessible, so the program director’s career stage also could be considered an advantage.