Writing Successful Proposals for Biological/Biomedical Experiments at LCLS

Regular User Proposals put forward experiments that are achievable within 12-60 hours of beamtime. Each proposal must focus on one specific experiment. Proposals should include discussions on scientific impact, feasibility, and success probability, as well as a clear shift-by-shift schedule. Re-submissions are allowed, but they do not receive preference. Multiple similar proposals from the same team will not be favored. Broader proposals must be re-submitted each cycle for peer review, and progress from previous beam times should be documented. 

Regular User Proposals are submitted through the Universal Proposal System

Protein Crystal Screening proposals (also known as Sample Testing) are for new users to gain beam time experience or test samples in half a shift (6 hours) before a full proposal. They must be submitted separately and follow a similar format to regular proposals. They should include the experimental team with names, institutions, emails, and relevant previous work. The scientific case must detail the background, significance, specific aims, and why LCLS is necessary. The experimental procedure should outline related LCLS proposals, supporting experiments, anticipated data rates, beam time plan, and additional equipment needed. Technical feasibility should cover required and additional equipment, experimental protocol, sample preparation, local facilities, and address safety concerns with necessary documents.

Protein Crystal Screening Proposals are submitted through the Universal Proposal System

The LCLS Rapid Access Program facilitates high-impact experiments with rolling reviews and quick scheduling. Proposals are accepted anytime during the Run cycle.  These experiments typically utilize Standard Configurations, as access is constrained and dependent on availability. Previous Rapid Access Program experiments were primarily structural biology experiments (e.g. COVID). Proposals must justify the urgent access to LCLS. 

Rapid Access Proposals are submitted through the User Portal

Regular User Proposal 

1. Table for Experimental Team
   • Demonstrates whether the team has sufficient expertise to perform the experiment
2. Scientific Case
   • Synchrotron data showing damage during data collection
   • Evidence that crystals are kinetically active
   • Time scales of kinetics
   • Computational results
3. Experimental Procedure
   • Time points guided by preliminary results
   • Pre-characterization of microcrystal activity for mix-and-inject or other non-static experiments
4. Technical Feasibility
   • Discussion on detectors, sample injectors, etc.
   • Required beamline parameters and standard configurations for the endstation
   • Photon energy and pulse length
   • Evaluation of whether the chosen endstation (MFX vs. CXI) meets experimental goals, including considerations of SNR improvement in vacuum vs. air and sample injection issues
   • Specific needs for CXI experiments, such as highest resolution for membrane proteins and 100 nm beam size
   • Importance of meeting and discussing with staff beforehand to solve feasibility questions and improve proposal quality
   • Support from facility staff required for lasers and mix-and-inject non-static experiments

Protein Crystal Screening

1. Scientific Question
   • Ensure the question is compelling and significant
   • Utilize PCS as an important intermediary step towards general proposal acceptance
2. Crystal Quality
   • Confirm the presence of crystals
   • Note that XFEL will not improve poorly diffracting crystals
3. Feasibility
   • Determine if the experiment is feasible at a synchrotron before proposing at XFEL
4. Resources
   • Refer to the LCLS Proposal Preparation Guidelines for detailed instructions on PCS proposals.

1. Scientific Impact
   • Does the proposal address a question that, if successfully answered, will have a strong impact on the scientific field or technological area?
2. Originality/New Scientific Field
   • Will the proposal open a new field or demonstrate a new approach in an existing field if successful?
3. Need for LCLS
   • To what extent is LCLS critical for the success of this proposal?
   • Can other techniques or facilities provide similar information about the scientific question?
4. Scientific Risk
   • Evaluate the probability that the proposed research will yield significant new results.
   • Balance the risk in the experimental portfolio, from high-risk/high-return investigations to lower-risk measurements of important systems.
5. Prior Results
   • Assess the success or progress of prior experiments, including precursor work at other facilities that motivate the need for LCLS.
6. Feasibility
   • LCLS scientists conduct a preliminary technical feasibility review of submitted proposals.
   • Engage with LCLS staff in preparing the proposal to help alleviate problems in this area.
7. Compatibility
   • Can the experiment be performed simultaneously with another experiment (e.g., with a monochromatic, hard X-ray beam)?
   • Does the experiment require significant modifications to an LCLS instrument setup?
   • Encourage proposals that use the declared “standard configurations” and can use monochromatic, hard X-ray beams to allow multiplexing between multiple experiments.

• Big picture: Early in the proposal, clearly communicate the exciting biological problem and how structural data from LCLS will uniquely address it, generating enthusiasm among PRP members who will advocate for your proposal. Begin with the bottom line: "What are we going to learn?" Be transparent with your characterization data; PRP members are screened for conflicts of interest and are not looking to scoop you. Explain why LCLS is the best facility for your science compared to others. Consider including whether the proposal has been submitted elsewhere.
• Team size: Some biology experiments typically require 3 researchers plus a data team, totaling 5 or more people, along with SED expert support. While the size of the team might be a barrier, PCS and rapid access programs help lower this barrier by increasing LCLS support. 
• Sample Considerations: The PRP requires you to demonstrate sample quality and LCLS-like characteristics, such as micron size and diffraction capabilities, as a fundamental requirement. To achieve this, use facilities like synchrotrons. If your samples are too small to test at a synchrotron, ensure you try them on a micron focus last-generation beam. Sample quality might still be a bottleneck, necessitating a larger team. When there's concern with sample quality, consider applying for crystal screening time instead of a full 5-shift proposal. This recommendation is a positive step, not a criticism, to ensure the best use of resources and enhance your experiment's success.
• For time-resolved or dynamic studies: It is essential to demonstrate that your sample is active in the crystal. Provide detailed information on timescales and ensure consistency with the delivery method.
• Methods Development: The PRP values proposals focused on method development and advancing XFEL science, recognizing their importance. Some PRP members are experts in methods, so it's crucial to clearly state the scientific question being addressed and the potential advancements for the XFEL bio community. Including a driving biological question in the proposal and correlating it to the method development is key.
• Preliminary Data: The amount of preliminary data needed can vary, and there is no set formula for writing a great proposal. However, perseverance is a crucial component in crafting a successful proposal.

Latest Proposal Schedule

Proposal Preparation Guidelines

MS Word

PDF

Proposal Example