2024 Sarafan ChEM-H Seed Grant

Overview

The most transformational human health research projects require expertise, techniques, and instrumentation not typically found in academia. To address these needs, Sarafan ChEM-H launched the Nucleus, a cluster of labs led by industry experts in areas like drug development,  structural biology, and clinical research who collaborate with Stanford labs. 

Sarafan ChEM-H is seeking proposals from Stanford labs who would like to start a new collaboration with a scientific team in the Nucleus.

We are accepting proposals for projects that would utilize one of the following research areas to pursue basic science and translational research projects:

• Medicinal Chemistry
• Metabolomics
• Macromolecular Structure
• Cryogenic Electron Microscopy
• High-Throughput Screening
• Protein Engineering

Successful projects will receive $50,000, which will be split between funds awarded to the PI lab and in-kind support. The award period will be 12 months, with the opportunity to request a 12-month no-cost extension. 

Deadline: 

All application materials must be received by 11:59 pm, Friday, January 17, 2025. Seed grant recipients will be notified by February 28, 2025. 

Apply here

Eligibility: 

Stanford faculty with UTL, UML, NTLR and CE appointments are eligible. CEs should provide a note from their Chair or Division Chief with their application stating that the Department/Division will cover salary support for time devoted to the project. Preference will be given to untenured faculty members. 

Faculty who have not yet collaborated with a Nucleus scientist, or those who have generated preliminary data and would like to jumpstart a larger-scale project are especially encouraged to apply.

What is the Nucleus?

The road from molecules to medicines, from discovery to translation, is complex. No single lab is equipped to address each hurdle on the path. The Nucleus at Sarafan ChEM-H is a cluster of labs that bring scientific expertise, tools, and flexibility to Stanford. Led by a unique cadre of industry-trained scientists, the groups at the Nucleus provide industry expertise, cutting-edge instruments and training to Stanford labs. From metabolomics to crystallography, from medicinal chemistry to cell therapies, the Nucleus supercharges research at Stanford.

Learn more at: https://chemh.stanford.edu/research/nucleus 

Support provided

Successful projects will receive $50,000, which will be split between support awarded to the PI lab in-kind support provided by the Nucleus. The split will be determined on a project-by-project basis. 

The PI lab support can cover direct costs for study-related expenses, including supplies, consumables, biobanking costs, etc. Student or postdoctoral scholar time can be supported on this award. Faculty and clinician time cannot be supported on this award.

In-kind support may include user training and instrument fees, and Nucleus scientist time. More details are included in the Research Areas section, below.

Before applying, each applicant is required to contact the leader of the relevant research area to discuss project scope and budget.

Proposal

Submit one PDF file containing the following in the order indicated below. All documents should be single-spaced, Arial 11 point font with 0.5” margins.

Proposals should be organized as follows:

1. Title page (1 page)
   1. Project Title
   2. Name of Nucleus research area that the project aims to leverage (Medicinal Chemistry, Metabolomics, Macromolecular Structure, Cryogenic Electron Microscopy, OR High-Throughput Screening)
   3. Name, title, and contact information for Principal Investigator(s)
   4. Name, title, and contact information of Primary Researcher (i.e. the student or postdoctoral scholar responsible for conducting the research and directly collaborating with Nucleus scientist(s))
2. Project Summary (½ page)
   1. Include in the summary a description of the problem you aim to solve and/or the the hypothesis you aim to test, the potential impact of the research, and how access to Nucleus scientists/facilities uniquely enables this research.
3. Project Narrative (2 pages)
   1. Background
      1. Please include a clear description of the problem you aim to solve and/or the the hypothesis you aim to test
   2. Goals/specific aims
   3. Project description
      1. Please include the ways in which access to Nucleus scientists and/or facilities uniquely enables this research.
4. References (1 page)
5. Proposed budget (½ page)
   1. Divide the budget into two sections, one for PI lab expenses and one for in-kind support provided by the Nucleus. 
   2. Note that project selection does not mean that the budget has been approved as proposed. Selected projects will undergo a more thorough financial evaluation and award terms will include approved budget with the split between support awarded to the PI lab and in-kind support clearly explained. Before applying, each applicant is required to contact the leader of the relevant research area to discuss project scope and budget.
6. Budget Justification (½ page)

Research Areas

Each application must identify one of the following research areas. Please read the descriptions below to ensure your proposal fits the criteria, and reach out the relevant group leader with questions about project feasibility. 

Medicinal Chemistry

Medicinal chemistry projects will include engineering one or more small molecule leads to improving their potency, selectivity, pharmacokinetics, and/or pharmacodynamics with the goal of identifying a high-quality, patentable drug prototype.

In-kind support will include access to the Medicinal Chemistry group to facilitate the design, synthesis, and screening of novel small molecules to identify lead drug prototypes.

Competitive projects will have already identified a well-characterized target. The proposal must identify at least one graduate student or postdoctoral scholar who can devote at least 25% time to the project. The student or postdoctoral scholar should expect to spend that time in the Nucleus lab space.

Medicinal Chemistry is led by Mark Smith (mxmith@stanford.edu). 

Metabolomics

Metabolomics projects will include the development, optimization, execution, and analysis of LC/MS assays for small molecules (i.e. metabolites and lipids) from biological samples, supporting both basic and clinical research. Projects with a strong therapeutic hypothesis that will lead to this discovery of new targets or the identification of new biomarkers for disease state are of particular interest.

In-kind support will include one-on-one training, collaboration, usage fees to access LC/MS instruments, and associated consumables. 

Competitive projects will identify at least one graduate student or postdoctoral scholar who will devote at least 15% time to the project. The student or postdoctoral scholar should expect to spend that time in the Nucleus lab space.

Metabolomics is led by Yuqin Dai (yuqindai@stanford.edu). 

Macromolecular Structure

Macromolecular structure projects will include the production, purification, and biophysical analysis of a protein of interest with the ultimate goal of determining three-dimensional structure using X-ray crystallography.

In-kind support will include one-on-one training and access to instrumentation at each stage of the protein production, purification, crystallization, and characterization, including:

• Hands-on protein production using the E. coli recombinant expression system and purification supported by chromatographic methods via Akta Pure Fast Protein Liquid Chromatography (FPLC).
• Biophysical analysis in solution: protein structure stability and oligomerization, thermal/chemical unfolding, and ligand binding affinity measurements through the NanoTemper Panta and Monolith Labelfree instruments.
• Advanced three-dimensional structure methodologies supported by automated liquid handling and crystal imaging, software for structure solving and refinement, and hands-on X-ray diffraction data acquisition at synchrotron macromolecular crystallography (MX) beamlines at SSRL/SLAC. 

Competitive projects will identify a protein sequence (or mutants of the parent sequence, paralogues, or orthologues) under 100 KDa molecular mass. Preferred targets are proteins that are poorly understood and lack sufficient structural data. Proposals will identify one graduate student or postdoctoral scholar who will devote at least 25% of the time to the project. The student or postdoctoral scholar should expect to spend that time in the Nucleus lab space.

Macromolecular Structure is led by Daniel Fernandez (danilo@stanford.edu). 

Cryogenic electron microscopy

Cryogenic electron microscopy (cryo-EM) projects will include cryoEM sample preparation, data acquisition and analysis of different types of samples, including biological or materials science contexts. 

In-kind support will include training and user access fees, sample preparation, associated consumables, and computational costs.

Competitive projects will identify at least one graduate student or postdoctoral scholar who will devote at least 15% time to the project. The student or postdoc will receive full-stack training including freeze cryoEM grids, microscope operation, and necessary coding/scripting skills required for data processing. 

The CryoEM group is led by Haoqing Wang (hwangab@stanford.edu). 

High-throughput screening

High-throughput screening projects will Include support for the development, optimization, and miniaturization of a biochemical or a cell-based assay in 384-well microplate format for use in high-throughput, small-molecule screening. 

In-kind support will include access to compound libraries, instrumentation fees, associated consumables, expert training, and advice in high-throughput assay development.

Competitive projects will identify at least one graduate student or postdoctoral scholar who will devote at least 20% time to the project. 

Competitive projects will have a well-characterized, novel target; reproducible in vitro assays and/or animal models; and a clear therapeutic hypothesis. 

The High-Throughput Screening Group is led by Bruce Koch (bkoch@stanford.edu). 

Protein engineering

Protein Engineering projects will include the selection of VL-based nanobodies by phage display. Optionally, the resulting clones (max. 5) will be fused to an Fc, produced and PA-purified. The clones will be analyzed for purity (PAGE, anal. SEC), binding (ELISA, SPR), cell binding and specificity (flow cytometry), and stability (DLS). 

In-kind support will include access to the Protein Engineering laboratory to perform panning, screening, and optionally, cloning, production, purification, and characterization. It will also include guidance and academic support from at least one member of the Protein Engineering laboratory.

Competitive projects will identify at least one graduate student or postdoctoral scholar who must spend 100% of their time for at least 4 weeks at the Protein Engineering laboratory for panning and screening. An additional commitment of 25% time for 4 weeks is expected for optional nanobody production and characterization. If the project is selected, the PI needs to bring the antigen in good quality (analytical SEC profile, biotinylated Avi-tag) and sufficient quantity (5 mg). If cell binding should be tested, a positive and negative cell line needs to be provided (>100,000 copies per cell). Every project will be analyzed by a member of the Protein Engineering laboratory for feasibility and necessary tools to be provided by the PI’s laboratory.

The Protein Engineering Group is led by Adrian Hugenmatter (adrian.hugenmatter@stanford.edu)  

Questions?

For general questions and questions related to the seed grant application process, please contact Rebecca McClellan (rmcclell@stanford.edu). 

For questions related to project scope, budget, and in-kind support, please reach out to the relevant scientific leader below: