Small Business Sources Sought: Nanobody production against endocytic proteins.

This is a Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. Large business may also provide responses to this notice. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition; and (4) availability of domestic sources manufactured in the United States in sufficient and reasonably available commercial quantities and of a satisfactory quality. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice. This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only. Background: The National Institutes of Health (NIH) is the nation's leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, conducting, supporting, and making medical discoveries that improve people's health and save lives. National Institute of Neurological Disorders and Stroke (NINDS) is one of 27 Institutes and Centers at the NIH, and its mission is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease for all people. The NINDS Synaptic Transmission Section (STS) combines physiological and cell-biological approaches to understand the mechanism and dynamics of cell membrane modulation during vesicle endocytosis. Various proteins orchestrate exo- and endocytosis in living cells at the nanometer scale. These events include vesicle docking and fusion, curvature generation, endocytosis, and others. NINDS STS characterizes these proteins, especially their spatial distribution and mechanisms of action in vivo with super-resolution imaging technique, and quantify several parameters related to their performance. Then NINDS STS wants to determine how these underlying mechanisms contribute to neurodevelopmental and neurodegenerative disorders, where synaptic signaling is severely impacted. Single-molecule localization microscopy is the most advanced super-resolution fluorescence imaging technique to identify cellular components and quantify various parameters. Over more than 20 years, NINDS STS has invested efforts to understand the molecular underpinnings of the synaptic transmission process. The most critical aspect of understanding synaptic transmission and associated pathologies is to explore how the vesicle recycling process is regulated at the synapse. Previous studies from STS lab and others have shown the involvement of thousands of proteins at the presynaptic terminal to form specialized regions and facilitate vesicle fission and fusion by avoiding molecular crowding. However, the specialized arrangements have never been visualized at the nerve terminal at the single-nanometer resolution, which is the actual molecular resolution. Therefore, much of the mechanistic regulation has remained as speculative ideas. While antibodies are the preferred choice of binders to identify endogenous proteins due to their simplicity and availability, the size of each antibody corresponds to about 8nm, while two antibodies used for immunocytochemistry would be around 16nm together. The current microscope in the lab can resolve up to 1-3nm. The dual antibody staining method would create a much larger (16nm) localization error. In addition, two large antibodies would create substantial molecular crowding in the already crowded synaptic environment, thus, creating artifacts and affecting quantification. The answer to these problems lies with the nanobodies or single-domain antibody binders due to their tiny size (<3nm) and customizability. The nanobodies are produced in Camelids, such as Alpacas, and are the ideal molecules for Single-molecule localization microscopy (SMLM) using the microscope in the lab. Thus, the nanobodies will be used to perform fluorescence imaging of endogenous proteins for identifying the nanoscale structures at the cell membrane and synaptic compartment and tracking the dynamics of a variety of cell-surface proteins regulating vesicle exocytosis and endocytosis in the cells during synaptic transmission and plasticity. Moreover, the nanobodies will be used to identify the nanoscale anatomy of endocytic machinery in chromaffin cells and nerve terminals. The nanoscale organization (also called the nano anatomy) of molecules and their spatial relationship regulate key aspects of vesicle fission-fusion and, thus, synaptic transmission. It is, therefore, essential to understand the operation of multiple proteins together in the cellular context to further the research on neurodevelopmental and neurodegenerative disorders. Purpose and Objectives: The NINDS STS requires the production of nanobodies against five (5) major endocytic proteins expressed in neurons to further the research on neurodevelopmental and neurodegenerative disorders. Project Requirements: Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities not otherwise provided by the Government as needed to perform the specific requirements provided in the DRAFT STATEMENT OF WORK. Period of Performance: The period of performance shall be seven (7) months from award. Capability statement /information sought. Companies that believe they possess the capabilities to provide the required products or services should submit documentation of their ability to meet each of the project requirements to the Contracting Officer. The capability statement must specifically address each of the project requirements separately. Additionally, the capability statement should include 1) the total number of employees, 2) the professional qualifications of personnel as it relates to the requirements outlined, 3) any contractor GSA Schedule contracts and/or other government-wide acquisition contracts (GWACs) by which all of the requirements may be met, if applicable, and 4) any other information considered relevant to this program. Capability statements must also include the Company Name, Unique Entity ID from SAM.gov, Physical Address, and Point of Contact Information. The response must include the respondents technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses. Interested companies are required to identify their type of business, applicable North American Industry Classification System (NAICS) Code, and size standards in accordance with the Small Business Administration. The government requests that no proprietary or confidential business data be submitted in a response to this notice. However, responses that indicate the information therein is proprietary will be properly safeguarded for Government use only. Capability statements must include the name and telephone number of a point of contact having authority and knowledge to discuss responses with Government representatives. Capability statements in response to this market survey that do not provide sufficient information for evaluation will be considered non-responsive. When submitting this information, please reference the notice number. One (1) copy of the response is required and must be in Microsoft Word or Adobe PDF format using 11-point or 12-point font, 8-1/2 x 11 paper size, with 1 top, bottom, left and right margins, and with single or double spacing. The information submitted must be in and outline format that addresses each of the elements of the project requirement and in the capability statement /information sought paragraphs stated herein. A cover page and an executive summary may be included but is not required. The response is limited to ten (10) page limit. The 10-page limit does not include the cover page, executive summary, or references, if requested. All responses to this notice must be submitted electronically to the Contract Specialist and Contracting Officer. Facsimile responses are NOT accepted. The response must be submitted to Renato Gomes, Contract Specialist, at e-mail address contact@example.gov. The response must be received on or before July 18, 2023, at 9:00 a.m., Eastern Time. - Disclaimer and Important Notes: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a presolicitation synopsis and solicitation may be published in www.sam.gov. However, responses to this notice will not be considered adequate responses to a solicitation. Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).