SOW Targeted quantitative metabolomics.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

Targeted quantitative metabolomics assays in brain and blood samples from a rat model of cognitive aging and human induced pluripotent stem cells (iPSCs) from APOE4/4 and APOE3/3 individuals.

Statement of Need and Purpose:

The Laboratory of Behavorial Neuroscience (LBN) recently identified a brain proteomic signature of incipient AD in young APOE ℇ4 carriers and nominated several promising drug targets implicating molecular perturbations occurring decades prior to the typical age at onset of AD. This work suggests early dysregulation in several biologic pathways in APOE ℇ4 carriers that may be causally related to the eventual accumulation of neuropathology and symptom onset in AD. Our prior work also suggests that this early dysregulation may overlap with age-associated cognitive impairment.

Background Information and Objective:

Traditional drug discovery approaches in Alzheimer’s disease (AD) have focused on modifying either amyloid plaque or neurofibrillary tangle pathologies that may be downstream of a disease cascade initiated years before these pathologies appear. These approaches have resulted in repeated failures of multiple pivotal phase-III clinical trials in patients with AD. Therefore identifying the earliest metabolic abnormalities in disease progression may be key to developing effective interventions.

The biological basis of cognitive resilience during aging remains poorly understood. Metabolic alterations in the brain and blood associated with preserved cognitive function during aging may help in better understanding such mechanisms.

The proposed study has two objectives. The first is to utilize a targeted quantitative metabolomics approach to assay human induced pluripotent (iPSC)- derived astrocytes, neurons and microglia from fibroblasts of APOE ℇ4 and APOE ℇ3 carriers. This rationale is to explore how the APOE ℇ4 may impact cell-type specific metabolic dysregulation; this will provide insight into molecular perturbations associated with APOE ℇ4 and identify potential drug targets.

The second objective is to utilize a targeted quantitative metabolomics approach to assay brain and blood tissue samples in a rat model of cognitive aging. The rationale is to explore regional brain metabolic changes in three groups of rats; aged-cognitively-impaired (AI), aged-cognitively-unimpaired (AU) and young unimpaired (YU). These studies will allow us to identify metabolic changes underlying cognitive resilience during aging and also identify potential drug targets that may help preserve cognitive function during aging.

Period of Performance:

September 30, 2022 – September 29, 2023

SCOPE OF WORK

General 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 Statement of Work below:

Specific Requirements:

The main objective of the requirement is but not limited to the following:

The Contractor shall perform quantitative targeted metabolomics assays on 36 (iPSC)-derived astrocytes, neurons and microglia from fibroblasts of APOE ℇ4 and APOE ℇ3 carriers., 30 rat blood plasma, and 30 rat brain samples (96 samples total) to measure the concentrations of small metabolites in the following classes:

i) Amino Acids, Acylcarnitines, Lipids, Hexoses, Biogenic Amines & Polyamines.

ii) Phosphatidylserines

iii) Phosphatidylglycerols

iv) Phosphatidyethanolamines

v) Ceramides

vi) Free oxysterols and cholesterol

vii) Free fatty acids

viii) Bile acids

LEVEL OF EFFORT:

Senior Researcher 960 labor hours for period of performance.

GOVERNMENT RESPONSIBILITIES

Provide adequate quantities of archived blood and brain tissue samples as well as (iPSC)-derived astrocytes, neurons and microglia to the contractor to enable the performance of the metabolomics assays detailed above.

DELIVERY OR DELIVERABLES

Electronic copy of excel spreadsheet incuding abolsute concentrations of all assayed metabolites in brain and blood samples to be delivered within 364 calendar days of receipt of samples by the contractor. The timely submission of this deliverable is essential to successful completing this requirement.

REPORTING REQUIREMENTS

The contractor shall provide written progress reports every 2 months for the contract period 9/30/22 through 9/29/23. The progress report shall cover all work completed during the specified period and shall present the work to be accomplished during the subsequent period.

This report shall also identify any problems that arose and a statement explaining how the problem was resolved. This report shall also identify any problems that have arisen but have not been completely resolved and provide an explanation.

Reports should be as follows;

Excel spreadsheet with absolute concentrations for metabolites listed above on all samples provided to the contractor

WORD document detailing all the technical aspects of the experimental methodology used including coefficients of variation (CV) of the assays, specimen usage, and success/failure rate of the assay.

OTHER CONSIDERATIONS

Travel:

N/A

Key Personnel:

The Contractor shall provide a dedicated point of contact to the government for the services.

Information System Security Plan:

Data Rights:

The National Institute on Aging shall have unlimited rights to and ownership of all deliverables provided under this contract including reports, recommendations, briefings, work plans and all other deliverables. This includes the deliverables provided under the basic contract and any optional task deliverables exercised by the contracting officer. In addition, it includes any additional deliverables required by contract change. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, “Definitions.” FAR clause 52.227-14, “Rights in Data-General, ” is hereby incorporated by reference and made a part of this contract/order.

Section 508—Electronic and Information Technology Standards:

The contractor is not required to develop, procure, maintain, or use Electronic and Information Technology (EIT) in the performance of the SOW.

Publications and Publicity:

Confidentiality of Information:

The government will not provide to the contractor any information or data of a personal nature about individual(s) or proprietary information or data pertaining to an institution or organization which is confidential.