CIRM SEED Grants (Scientific Excellence through Exploration and Development)

CIRM SEED Grants (Scientific Excellence through Exploration and Development) is sponsored by California Institute for Regenerative Medicine (CIRM). This program funds preliminary research in the biology, derivation, and application of human embryonic stem cells (hESCs) and their derivatives, ground-breaking exploratory concepts, and aims to attract new investigators to the field of hESC research.

The first CIRM research grant initiative, Innovation in Human Embryonic Stem Cell Research , is intended to “jump-start” hESC research in California.

It will be carried out through three Requests for Applications (RFAs), two for individual investigator projects and one for institutional shared laboratory space: RFA 06-01: CIRM SEED Grants RFA 06-02: CIRM Comprehensive Grants RFA 06-03: CIRM Shared Research Laboratory Grants and Stem Cell Techniques Course The CIRM SEED Grant RFA is the first of these three.

OBJECTIVE OF THE CIRM SEED GRANT PROGRAM – RFA 06-01 The SEED (Scientific Excellence through Exploration and Development) Grant Program is intended to bring new ideas and new investigators into the field of human embryonic stem cell (hESC) research and will offer an opportunity for investigators to carry out studies that may yield preliminary data or proof -of -principle results that could then be extended to full scale investigations.

The goals of the program are (1) to fund preliminary research in the biology, derivation, and application of hESCs and their derivatives, (2) to fund ground-breaking, exploratory new concepts and approaches in the field, and (3) to attract new investigators – young investigators as well as established scientists in other fields – to direct their focus to hESC research.

This RFA is open to all academic and non-profit research institutions in the state of California. Future solicitations may be available to for-profit institutions when the CIRM Intellectual Property Policy for for-profit organizations is in place.

Scientists with a record of accomplishment in hESC research or closely- related stem cell fields who have extensive preliminary data may choose to apply for a CIRM Comprehensive Research Grant (RFA 06-02) to conduct or expand promising on-going research using hESCs. Investigators may apply for either a SEED grant or a Comprehensive Research grant, but not both .

CIRM will accept only one application per Principal Investigator (PI) for one or the other RFA. This solicitation is limited to proposals that work directly on hESCs and that can utilize existing space and major equipment at the applicant institution. Funding will be provided for Project costs and other related costs as described in the CIRM Grants Administration Policy .

Project costs of up to $200,000 per year for up to 2 years may be requested. The allowable Indirect Costs for this RFA are limited to 25% as described in the CIRM Grants Administration Policy (GAP) . Principal Investigators (PIs) may be either senior or junior faculty and must be full- time employees of the grantee organization.

A minimum 5% of the PI’s total effort must be devoted to the project. Post-doctoral fellows may not apply directly to this program or serve as the PI. The following are examples of hESC research that are expected to be encompassed within this RFA; applications for other innovative projects will also be considered and are strongly encouraged.

Development of new technology and conditions to optimize the derivation, self-renewal, maintenance, stability, and/or cryopreservation of hESCs. Derivation of disease-specific hESC lines Characterization and comparison of different hESC lines.

Understanding the regulation of self-renewal and fate decisions Targeting lineage-specific differentiation of hESCs Assessing the fates of hESCs and their derivatives in animal models of disease Assessing the tumorigenicity of hESCs and their derivatives. Reprogramming of adult human somatic cell nuclei or the use of other novel techniques to generate hESCs. CIRM expects to commit up to $24 million over a two year period for this RFA.

The Institute anticipates that approximately 30 SEED grants will be awarded for a period of no more than two years each. CIRM reserves the right to discontinue or change funding levels from year to year if significant scientific progress is not demonstrated. All allowable costs for research grants are detailed in the CIRM GAP .

Salaries for key personnel providing services to the grant. This may include the Principal Investigator, research associate, and/or technical support salaries, based on percent of full time effort commensurate with the established salary structure of the applicant institution.

Because CIRM considers pre-doctoral, post-doctoral and clinical fellows as trainees and not as employees, institutions may request stipend, health insurance and allowable tuition and fees as costs for trainees. Administrative support salaries are expected to be covered by the Indirect Costs for the grant.

Equipment and Supplies Major equipment necessary to conduct the research proposed must be available at the applicant institution (see definition of equipment in the CIRM GAP). Minor equipment purchases ( Travel Recipients (PIs) of CIRM SEED Grants are expected to attend an annual CIRM-organized meeting for grantees in California and should include in the budget costs for travel to this meeting.

Travel costs associated with collaborations necessary to perform the project activities are allowable. Details of allowable travel costs can be found in the CIRM GAP. All institutions and investigators planning to apply for a CIRM SEED Grant must notify CIRM with a letter of intent (LOI) by September 15, 2006 .

The letter should describe concisely the overall goals and technical approaches of the proposed research. A list of proposed collaborators with their institutional affiliations should be included. In order to facilitate planning for the review of the application, please identify in the LOI the types of expertise needed to evaluate the proposal.

Letters of intent are non-binding, but applications will not be accepted if such a letter has not been provided to CIRM by the deadline. Letters of intent must be sent as an email attachment to loi@cirm. ca.

gov . Full Application Instructions All applications for CIRM SEED Grants must be received by October 13, 2006 . Only applicants who have sent in an LOI will be allowed to submit an application.

Applicants must use the CIRM SEED Grant Application Form which will be available on the CIRM website by September 15, 2006. The application for SEED Grants includes: Abstract (up to 3000 characters): State the goals of the proposal; summarize the overall plans of the research proposed and how it will meet the stated objectives of the proposal. Describe the rationale for these studies and techniques you will use to pursue these goals.

Explain the likelihood of this proposal being funded by the federal government. Public Abstract (up to 3000 characters): Briefly describe in lay language the proposed research and how it will, directly or indirectly, contribute to the development of diagnostics, tools or therapies.

This Public Abstract will become public information; therefore, do not include proprietary or confidential information or information that could identify the applicant (P. I. and home institution).

Statement of Benefit to California (up to 3000 characters): Describe in a few sentences how the proposed research will benefit the state of California and its citizens. This Statement of Benefit will become public information; therefore, do not include proprietary or confidential information or information that could identify the applicant (P. I.

and home institution). Specific Aims (up to 1 page): Explain the broad, long-term objectives and the goal of the specific research proposed, e.g., to test a stated hypothesis, create a novel design, solve a specific problem, challenge an existing paradigm or practice, develop a new therapy, address a critical barrier to progress in the field, or develop new technology.

Identify and enumerate each specific aim of the proposal, in a concise and step-wise fashion, and how that will lead to the broad goal of this research. Explain the likelihood of this proposal being funded by the federal government. Rationale and Significance (1-2 pages): Summarize the context and background of the present application and the specific rationale for the work proposed.

Evaluate existing knowledge and specifically identify the gaps that the project is intended to fill. State how the proposed research meets CIRM’s goals of funding innovative, perhaps scientifically risky and untested research. If the aims of the application are achieved, state how this information will contribute to the development of diagnostics and/or therapies based on stem cell research.

Research Design and Methods (up to 3 pages): Describe concisely, but in sufficient detail to permit evaluation of the merit of the research, the experimental design, methods and techniques to be employed to achieve the goals specified in the proposal. Identify the new or risky aspects of the research, anticipated pitfalls, and plans to overcome or circumvent difficulties that may arise.

Describe the methods of analysis of results, including criteria for success of the preliminary studies. Feasibility (up to 2 pages): Provide any information that will help to establish the experience and competence of the investigator to pursue the proposed project. It is not necessary to have preliminary data relevant to the proposed research, since generation of such data is the primary purpose of the CIRM SEED Grant Program.

Collaboration (up to 1 page): If collaboration is integral to the success of the project, describe how this will be achieved. Timeline (1/2 page): Provide a realistic timetable for completing each proposed specific aim of the project; where appropriate provide specific milestones for evaluating the achievement of each specific aim. References (up to 2 pages): List all references used in the body of the proposal.

Laboratory/Clinical Facilities including major equipment (1/2 page): Provide a short description of the facilities and environment in which the work will be done, and the major equipment and resources available for conducting the proposed research. Discuss ways in which the proposed studies will benefit from unique features of the scientific environment or employ useful collaborative arrangements where applicable.

Key Personnel: List the scientific participants and their roles in the proposed research in the relevant section of the application form, regardless of whether they will receive salary support from the grant. These may include the Principal Investigator, co-investigators, research associates, technicians and trainees (students and fellows).

For each key scientific personnel listed, provide a 2 page biographical sketch that highlights prior stem cell (especially hESC) research experience and/or special skills related to the proposed research. Include relevant publications. Budget : Provide all budget information requested in the budget section of in the application form.

CIRM SEED grant applications will be reviewed by the Scientific and Medical Research Funding Working Group (SMRFWG) of CIRM. The SMRFWG consists of fifteen basic and clinical scientists from institutions outside California, seven patient advocates who are members of the Independent Citizen’s Oversight Committee (ICOC), and the Chair of the ICOC. The membership of the SMRFWG is available here .

The ICOC was established by the California Research and Cures Act (Proposition 71) to oversee CIRM and is responsible for all final funding decisions. The composition of the ICOC is available here . Fifteen scientists on the SMRFWG will review the applications and rate them according to scientific and technical merit.

The following are among the qualities to be considered for evaluation of research grant applications. For SEED grants, particular emphasis will be placed on innovation and quality of the research plan . Impact and Significance Does the research address an important problem?

Will the proposed research significantly move the field forward, either scientifically or medically? Innovation Is the approach original? Does it bring novel ideas, technologies or strategies to bear on an important problem in hESC research?

Does it break new ground? Quality of the Research Plan Is the research carefully planned to give a meaningful result? Are the possible difficulties acknowledged, with alternative plans should the proposed strategy fail?

Is the timetable for achieving significant results reasonable? Feasibility Can the aims of the research be reasonably achieved? Do the investigators have the training and experience to conduct the proposed project?

Does the investigator have access to appropriate technology to perform the research? Collaboration Does the proposal support collaborative efforts, and if so, to what extent does the collaboration enhance the quality and potential of the research proposed? Responsiveness to the RFA How is the proposal responsive to the criteria and objectives stated in the RFA?

Eligibility for Federal funding Is the research ineligible or unlikely to receive federal funding? If not, is the research sufficiently compelling in that it presents “a vital research opportunity” that will materially aid the objectives of CIRM? Recommendations for funding will then be made by the full SMRFWG to the ICOC.

In making these recommendations, the SMRFWG will review the entire portfolio of applications, taking into consideration the following criteria: Scientific and technical merit. Appropriate balance between innovation and feasibility. Where relevant, the appropriate balance between fundamental research, therapy development and clinical application.

Where relevant, the appropriate balance and range of diseases addressed. Other considerations from the perspective of patient advocates. All SEED Grant applications must be submitted to CIRM by October 13, 2006 .

The application form for CIRM SEED Grants will be available on the CIRM website by September 15, 2006. Send a PDF file of the full application to SEED@cirm. ca.

gov . In addition to submitting the application electronically, send a signed original of the completed application to CIRM. The hardcopy must be signed by both the PI and the institution’s authorized organizational official.

Mail the signed hardcopy to: California Institute for Regenerative Medicine Receipt of letters of intent: September 15, 2006 Receipt of full application: October 13, 2006 Review of applications: November-December, 2006 Review by ICOC: February, 2007 Announcement of awards: March 2007 Earliest funding of awards: March, 2007 Scientific Review Officer California Institute for Regenerative Medicine Email: gsambrano@cirm. ca.

gov For programmatic information : Scientific Program Officer California Institute for Regenerative Medicine Email: polson@cirm. ca.

gov Director of Scientific Activities California Institute for Regenerative Medicine CIRM Grants Administration Policy: CIRM’s governing board, the ICOC, adopted an Interim Grants Administration Policy (GAP) for Academic and Non-profit Institutions that describes the standard terms and conditions of grant awards issued by the Institute. All research conducted under this award will be expected to comply with the stated policy .

CIRM reserves the right to discontinue or change funding levels from year to year if significant scientific progress has not been demonstrated. Human Stem Cell Research Regulations: CIRM has adopted medical and ethical standards for human stem cell research. All research conducted under this award will be expected to comply with these standards .

While these regulations prohibit donors of gametes, embryos, somatic cells or human tissue from receiving valuable consideration for their donation, they do allow for reimbursement for permissible expenses as determined by an IRB.

“Permissible Expenses” means necessary and reasonable costs directly incurred as a result of donation participation in research activities and may include costs such as those associated with travel, housing, child care, medical care, health insurance and actual lost wages.

For research activities proposing to obtain gametes, embryos, somatic cell or human tissue from human subjects, CIRM requires the applicant to submit, at the time of application, their reimbursement policy describing how they intend to calculate permissible expenses.

Intellectual Property Policy for Non-profit Organizations: CIRM has adopted policies that govern the intellectual property created under grant awards issued by CIRM to non-profit organizations. Research conducted under this award will be expected to comply with the terms and conditions stated in this policy .

University of California, Irvine Dr. Kyoko Yokomori Derivation and characterization of human ES cells from FSHD embryos University of California, Davis Dr. Ebenezer N Yamoah Hair Cells and Spiral Ganglion Neuron Differentiation from Human Embryonic Stem Cells University of California, San Francisco Dr. Holger F Willenbring Induction of pluripotency in fibroblasts by fusion with enucleated human embryonic stem cell syncytia University of California, San Francisco Dr. Thea D.

Tlsty PhD Role of the tumor suppressor gene, p16INK4a, in regulating stem cell phenotypes in embryonic stem cells and human epithelial cells.

University of California, Irvine Dr. Vincent Procaccio Mitochondrial Dysfunction in Embryonic Stem Cells University of California, Irvine Dr. Grant R MacGregor Production of Oocytes from Human ES Cells University of California, Irvine Thomas Edward Lane Human Embryonic Stem Cells and Remyelination in a Viral Model of Demyelination Stanford University Dr. Aaron J Hsueh Patient-specific cells with nuclear transfer University of California, Los Angeles Dr. Noriyuki Kasahara Down-Regulation of Alloreactive Immune Responses to hES Cell-Derived Graft Tissues Stanford University Dr. Joseph C.

Wu In Vivo Imaging of Human Embryonic Stem Cell Derivatives and Tumorigenicity University of California, San Diego Dr. Binhai Zheng Dr. Genetic manipulation of human embryonic stem cells and its application in studying CNS development and repair Sanford Burnham Prebys Medical Discovery Institute Dr. Zhuohua Zhang Modeling Parkinson’s Disease Using Human Embryonic Stem Cells Stanford University Kenneth Weinberg Embryonic stem cell-derived thymic epithelial cells University of Southern California Dr. Qilong Ying Self-renewal of human embryonic stem cells University of California, Davis Professor A.

Hari Reddi hESCs for Articular Cartilage Regeneration University of California, Los Angeles Dr. Hanna Mikkola Improving microenvironments to promote hematopoietic stem cell development from human embryonic stem cells University of California, Berkeley Ellen Robey In Vitro Differentiation of T cells from Human Embryonic Stem Cells. Sanford Burnham Prebys Medical Discovery Institute Dr. Robert G.

Oshima Trophoblast differentiation of human ES cells. Salk Institute for Biological Studies Dr. Samuel L Pfaff Gene regulatory mechanisms that control spinal neuron differentiation from hES cells.

University of California, Los Angeles William Lowry Modeling Human Embryonic Development with Human Embryonic Stem Cells University of California, Irvine Dr. Frank LaFerla Development of human ES cell lines as a model system for Alzheimer disease drug discovery University of California, Los Angeles Dr. Siavash Kurdistani Cellular epigenetic diversity as a blueprint for defining the identity and functional potential of human embryonic stem cells Stanford University Dr. Mark Kay Dr. Novel vectors for gene transfer into human ES cells Sanford Burnham Prebys Medical Discovery Institute Professor Ziwei Huang New Chemokine-Derived Therapeutics Targeting Stem Cell Migration University of Southern California Dr. David R.

Hinton Therapeutic potential of Retinal Pigment Epithelial cell lines derived from hES cells for retinal degeneration. Stanford University Dr. Susan K McConnell Optimization of guidance response in human embryonic stem cell derived midbrain dopaminergic neurons in development and disease Gladstone Institutes, J.

David Dr. Warner C Greene The APOBEC3 Gene Family as Guardians of Genome Stability in Human Embryonic Stem Cells University of California, Los Angeles Dr. Zoran Galic Genetic Enhancement of the Immune Response to Melanoma via hESC-derived T cells University of California, San Diego Dr. Anirvan Ghosh Dr. Generation of forebrain neurons from human embryonic stem cells Salk Institute for Biological Studies Dr. Senyon Choe A method to maintain and propagate pluripotent human ES cells University of California, San Diego Shu Chien Combinatorial Platform for Optimizing Microenvironments to Control hESC Fate University of California, Los Angeles Dr. Irvin SY Chen Genetic modification of the human genome to resist HIV-1 infection and/or disease progression University of California, Los Angeles Dr. Michael A.

Teitell Role of Mitochondria in Self-Renewal Versus Differentiation of Human Embryonic Stem Cells Sanford Burnham Prebys Medical Discovery Institute Dr. Huei-sheng Vincent Chen Development of Neuro-Coupled Human Embryonic Stem Cell-Derived Cardiac Pacemaker Cells.

University of California, Santa Cruz Dr. David Andrew Feldheim Assessing the role of Eph/ephrin signaling in hESC growth and differentiation Sanford Burnham Prebys Medical Discovery Institute Dr. Gregg Duester Retinoic Acid-FGF Antagonism during Motor Neuron Differentiation of Human ES Cells University of California, Irvine Professor Charles L Limoli Using human embryonic stem cells to treat radiation-induced stem cell loss: Benefits vs cancer risk Stanford University Dr. Phillip C Yang In Vivo Molecular Magnetic Resonance Imaging of Human Embryonic Stem Cells in Murine Model of Myocardial Infarction Gladstone Institutes, J.

David Dr. Fen-Biao N.

Gao MicroRNAs in Human Stem Cell Differentiation and Mental Disorders University of California, San Francisco Dr. Valerie Marie Weaver Force, Dimensionality and Stem Cell Fate Stanford University Dr. Joanna Wysocka PhD Role of Chromatin Modifiers in Regulating Human Embryonic Stem Cell Pluripotency Stanford University Dr. Thomas Wandless Reprogramming Differentiated Human Cells to a Pluripotent State Sanford Burnham Prebys Medical Discovery Institute Dr. Alexey V.

Terskikh Analysis of Candidate Neural Crest Cells Derived from Human ES Cells University of Southern California Dr. Peter W Laird Screening for Oncogenic Epigenetic Alterations in Human ES Cells Stanford University Dr. John P.

Cooke EC regeneration in cerebrovascular ischemia: role of NO University of California, Berkeley Dr. Carolyn R Bertozzi Profiling surface glycans and glycoprotein expression of human embryonic stem cells The Regents of the University of California on behalf of its Riverside Campus Dr. Frank Sauer Non-coding RNA as tool for the active control of stem cell differentiation University of California, San Francisco Dr. Miguel Ramalho-Santos Transcriptional Regulation of Human Embryonic Stem Cells City of Hope, Beckman Research Institute Dr. Timothy R.

O’Connor Sources of Genetic Instability in Human Embryonic Stem Cells. University of California, San Francisco Dr. Heike E Daldrup-Link Labeling of human embryonic stem cells with iron oxide nanoparticles and fluorescent dyes for a non-invasive cell depiction with MR imaging and optical imaging University of California, Irvine Dr. Brian J.

Cummings The Immunological Niche: Effect of immunosuppressant drugs on stem cell proliferation, gene expression, and differentiation in a model of spinal cord injury. Gladstone Institutes, J. David Dr. Eric Verdin Role of HDAC in human stem cells pluripotentiality and differentiation University of California, San Francisco Dr. Didier Y Stainier Endodermal differentiation of human ES cells Scripps Research Institute Peter G.

Schultz A Chemical Approach to Stem Cell Biology Stanford University Dr. Julien Sage Functions of RB family proteins in human embryonic stem cells Ludwig Institute for Cancer Research Dr. Bing Ren Mapping the transcriptional regulatory elements in the genome of hESC The Regents of the University of California on behalf of its Riverside Campus Professor Michael C Pirrung Stem Cell Survival and Differentiation Through Chemical Genetics University of Southern California Dr. Wange Lu Regulation of human neural progenitor cell proliferation by Ryk-mediated Wnt signaling University of California, San Diego Dr. Cornelis Murre Generation of long-term cultures of human hematopoietic multipotent progenitors from embryonic stem cells Children’s Hospital of Los Angeles Dr. Elizabeth Rachel Lawlor hESC as tools to investigate the neural crest origin of Ewing’s sarcoma Stanford University Dr. Calvin Jay Kuo Differentiation of Human Embryonic Stem Cells to Intestinal Fates Stanford University Dr. Krishna Shenoy Technology for hESC-Derived Cardiomyocyte Differentiation and Optimization of Graft-Host Integration in Adult Myocardium University of California, Merced Dr. Michelle Khine Micro Platform for Controlled Cardiac Myocyte Differentiation University of California, Irvine Dr. Michelle Khine Micro Platform for Controlled Cardiac Myocyte Differentiation University of California, San Diego Dr. Catriona Jamieson Derivation and Characterization of Cancer Stem Cells from Human ES Cells University of California, San Francisco Dr. Su Guo Identifying small molecules that stimulate the differentiation of hESCs into dopamine-producing neurons University of California, San Francisco Dr. Linda C.

Giudice Human Embryonic Stem Cell Differentiation to Trophoblast: Basic Biology and Clinical Translation to Improve Human Fertility University of California, San Francisco Dr. Robert Blelloch Dr. MicroRNA Regulation of Human Embryonic Stem Cell Self-Renewal and Differentiation Sanford Burnham Prebys Medical Discovery Institute Dr. Hudson Freeze Role of Glycans in Human Embryonic Stem Cell Conversion to Neural Precursor Cells University of California, San Diego Dr Sylvia Evans Specification of Ventricular Myocyte and Pacemaker Lineages Utilizing Human Embryonic Stem Cells Salk Institute for Biological Studies Dr. Beverly M Emerson Dr. Regulation of Specific Chromosomal Boundary Elements by CTCF Protein Complexes in Human Embryonic Stem Cells University of California, Santa Cruz Dr. Bin Chen In vitro differentiation of hESCs into corticospinal motor neurons Human BioMolecular Research Institute Dr. John R Cashman Ph.

D. Discovering Potent Molecules with Human ESCs to Treat Heart Disease Buck Institute for Age Research Dr. Dale E. Bredesen Programmed Cell Death Pathways Activated in Embryonic Stem Cells