Somnus

Special Notice DARPA-SN-23-40Defense Advanced Research Projects Agency (DARPA) / Biological Technologies Office (BTO)Research Opportunity: SomnusI. INTRODUCTIONThis announcement describes a research thrust, entitled Somnus, that will focus on the identification of molecules and mechanisms of host interactions with the gut microbiome that are associated with the restorative effect of sleep on cognitive performance. This solicitation is released under the current DARPA BTO Office Wide Broad Agency Announcement (BAA), HR001122S0034, entitled “Biological Technologies,” which can be found at the URL below:https://sam.gov/opp/4f70483c0b4b49aeac299342a36af04d/viewThis special notice is soliciting proposal abstracts and full proposals to HR001122S0034. It is highly encouraged that proposers submit proposal abstracts (2 pages maximum), which will be reviewed to determine whether or not

a full proposal submission is encouraged. The requirements for the abstract and full proposal submission, evaluation, and award of any resulting contracts will ultimately be subject to the terms described in HR001122S0034.The purpose of this announcement is (1) to draw the attention of the scientific community to the Somnus study topics, (2) to initiate dialogue and teaming that will lead to team-based abstract/proposal submissions to address the Somnus study topics, (3) to share the planned timetable for the submission of abstracts and government feedback concerning said abstracts, and (4) to share the planned timetable for the submission of full proposals.• Webinar Date: March 28, 2023• Proposal Abstract Due Date: April 17, 2023• Full Proposal Due Date: June 1, 2023II. TOPIC DESCRIPTIONDARPA is soliciting proposals for research aimed at identifying molecules and mechanisms of host interactions with the gut microbiome that are associated with the restorative effect of sleep on cognitive performance. To achieve this goal, funded studies will utilize an animal model of acute sleep deprivation and recovery, along with a variety of approaches to collect biospecimens for measurement and analysis. Proposals should include descriptions of optional tasks, that, if exercised, will include analysis of previously collected (i.e., banked) blood biospecimens obtained from humans undergoing an acute sleep deprivation protocol and comparing results with animal data collected during the Base Period.Overview – Somnus:Insufficient sleep is highly prevalent in the military and has multiple causes ranging from environmental factors to disease processes. According to a recent DoD study, 64% of US service members reported less than seven hours of sleep per night, compared to 28-37% of adults in civilian population. Irrespective of its etiology, sleep loss has negative effects on health and performance that are poorly addressed by existing therapeutic interventions. Acute sleep loss has been found to result in cognitive and social dysfunction, as well as dysregulation of molecular pathways underlying immune and metabolic function. While negative effects of acute loss may be restored by follow-on recovery sleep, achieving effective recovery sleep may be stymied by2 suboptimal environmental or disease-related conditions, leading to chronic sleep loss. The deleterious effects of chronic sleep loss are systemic and include metabolic dysregulation (insulin resistance, diabetes, and obesity), immune dysfunction (increased risk of infection, neurodegeneration, and autoimmune diseases) and neuropsychiatric disorders (PTSD, depression, and increased risk of suicide). Furthermore, sleep restriction reduces the ability to execute complex cognitive tasks, effective communication, rapid decision making, and maintenance of vigilance and alertness required to carry out assigned duties.The propensity to sleep and the subjective experience of sleepiness accumulate with increased time spent awake, but the biological mechanisms regulating this drive to sleep, or “sleep pressure,” have not been characterized. Recent studies have identified various changes in gut microbiota associated with sleep deprivation and/ or insomnia in humans, as well as in animal models. Evidence suggests that the gut microbiomes of insomnia patients compared to healthy controls are characterized by lower microbial richness and diversity, as well as depletion of anaerobes and short-chain fatty acid (SCFA)-producing bacteria. Additionally, gut bacterial metabolites and components of the bacterial cell wall have been shown to serve in sleep signaling through peripheral pathways, such as the hepatoportal vein and the vagus nerve. Notably, however, these observed associations have not been tied to changes in functional outcome measures associated with cognitive function following sleep deprivation. Thus, it is unknown whether such observed changes in the gut ecological environment lead to deleterious effects of sleep deprivation on health and performance, or whether they are involved in compensatory mechanisms to recover physiological function following sleep deprivation. Moreover, while studies have suggested that modulating the gut microbiome via mechanisms such as administration of prebiotics, butyrate (a gut bacterial metabolite) or lipopolysaccharide (a bacterial cell wall component) can modulate sleep/wake states in animal models, the underlying mechanisms have not been fully elucidated, and the impacts of these interventions on health and functional performance following sleep deprivation have not yet been explored.Somnus seeks to identify molecules and mechanisms of host interactions with the gut microbiome that are associated with the restorative effect of sleep on cognitive performance in an animal model. If successful, the study may pursue additional efforts to identify similarities and differences between humans and animals in relative concentrations of circulating biomolecules associated with sleep pressure and cognitive outcomes across acute sleep deprivation and recovery.Objective:DARPA is interested in revolutionary research ideas to assess and modulate the impact of gut microbiota on sleep-wake states and cognitive function across acute sleep deprivation and recovery according to the following 17-month structure. The Somnus study is divided into a base period of performance of 13 months and an option period of 4 months as described below:Base Period: DARPA seeks to identify gut microbiota and downstream biomolecules (e.g., metabolites, lipids, peptides, nucleic acids, etc.) associated with acute sleep deprivation and recovery. Additionally, DARPA is interested in characterizing differences in gut microbiota and associated biomolecules – including circulating molecules detectable in blood samples – corresponding to inter-individual variability in the physiological, behavioral, and cognitive effects of sleep pressure as it fluctuates between deprived and recovered states.At the conclusion of the Base Period effort, performers will deliver a list of identified molecules that could be exploited to modulate physiological underpinnings of the cognitive response to changes in sleep pressure.Options: There are two separate option tasks that, if DARPA elects to proceed with both, may be executed in parallel with one another.Option 1: Should the first option task be executed, performers will conduct extended, system-level analyses of datasets obtained in the Base Period, with the goal of identifying putative molecular/biochemical pathways associated with host-microbiome interaction in the gut and resultant molecules in the blood that correspond to sleep pressure and its effects on cognitive function.Option 2: Should the second option task be executed, the government will provide a previously collected dataset at the start of this task that includes blood samples and cognitive performance measures collected prior to and following a period of acute sleep deprivation across a cohort of approximately thirty (30) participants. The goal of this option is to verify that molecules, or their homologs, identified during the Base Period of Somnus, correspond to changes in sleep pressure in humans.Anticipated Structure:The Somnus study duration is 17 months. The period of performance (PoP) includes obtaining local Institutional Animal Care and Use Committee (IACUC) and U.S. Army Medical Research and Development Command Animal Care and Use Review Office (ACURO) approvals as well as successfully identifying molecules and mechanisms of host interactions with the gut microbiome that are associated with the restorative effect of sleep on cognitive performance in an animal model. Should Option 2 be exercised, the PoP also includes obtaining local Institutional Review Board (IRB) and U.S. Army Medical Research and Development Command Office of Human Research Oversight (OHRO) approvals to analyze a previously collected dataset of biospecimens provided by the government, in order to identify circulating biomolecules associated with sleep pressure and cognitive function prior to and following acute sleep deprivation, if required.Proposers shall develop a milestone-driven work plan, incorporating metrics and deliverables into the 17-month period of performance. Proposals should include measurement methodology (devices, collection approach, etc.) for achieving the Somnus study goals according to the timeline shown in Fig. 1.Periodic milestones will direct efforts to meet the final goal of the Somnus study. A minimum set of these milestones are described below in the context of key tasks associated with Somnus goals. Proposals should describe any additional milestones required to achieve the study goals and the milestones described below. For example, additional milestones may include a timeframe for completing multiomic analysis of blood and fecal biospecimens to achieve data analysis goals before or by the end of the Base Period.Throughout this document, “multiomic analysis” refers to chemical and genomic methods of processing the collected biospecimens, and “data analysis” refers to computational methods of identification, characterization, and interpretation of multiomic raw data outputs.Fig. 1. Somnus study timeline.Base Period (13 Months): Identify gut microbiota, associated biological molecules, and molecular pathways associated with sleep pressure and cognitive function in the context of acute sleep deprivation and recovery in an animal model. The Base Period will consist of two main tasks.Task 1 (1 MAC – 13 MAC): Obtain required protocol approvals (IACUC & ACURO) for all animal studies to be conducted during the Base Period. Animal use protocols must describe how the performer plans to study acute sleep deprivation and restorative sleep in both optimal and suboptimal (e.g., noisy or stressful) conditions in an animal model. Acquire biospecimens and other physiological measures across sleep deprived and non-sleep deprived states in an animal model to identify changes in the relative abundance and/or activity of gut microbial species, as well as increases or decreases in circulating molecules attributable to gut microbiota in response to changes in sleep pressure (i.e., recovery from fatigue due to sleep restriction) and resulting cognitive function. Task 1 involves data collection from animal models only; any proposed efforts to collect human data will be considered out of scope. To reduce potential gaps in data collection between the Base and Option Periods, Task 1 involves submission of human use protocols in preparation for potential execution of Option 2, which includes analysis of a government-provided human dataset (see Option 2 description below for additional detail). Task 1 must include, at least, the following milestones:Month 1: Submit animal use protocol packages for IACUC review and approval.Month 2: Upon receipt of IACUC approval, submit animal use protocol packages for ACURO review and approval.Month 4: Upon receipt of ACURO approval, begin collection of biospecimens and other physiological measures across sleep deprived and non-sleep deprived states.Month 8: Acquire biospecimens from the gut microbiome and blood within-subjects across periods of acute sleep deprivation and recovery in an animal model.o Obtain physiological measures associated with changes in sleep pressure over the course of acute sleep deprivation.o Quantify physiological correlates of recovery sleep in response to acute sleep deprivation.o Assess behavioral performance on cognitive tasks across baseline and acute sleep deprivation conditions, as well as following recovery sleep.o Collect biospecimens from animals across baseline, sleep deprivation, and recovery sleep conditions, including whole blood, fecal samples, or comparable specimens.o Collect additional biospecimens from animals after recovery sleep including luminal fluid, intestinal tissue, or comparable specimens.Month 10: In preparation for potential execution of Option 2, submit IRB packages for research protocols involving analysis of blood biomarkers in human datasets furnished by the government.Month 11: Upon receipt of IRB approval, submit human use protocol packages for OHRO review and approval for potential Option 2 efforts involving analysis of blood biomarkers in human datasets furnished by the government.Month 13: Finalize test plan for Option 2 to include planned analytical approaches and pipeline.Task 2 (7 MAC - 13 MAC): Perform multiomic analysis of biospecimens (transcriptomics/metatranscriptomics, metagenomics, proteomics, and/or metabolomics) to identify molecules that arise from interactions between the host and microbiome and correlate with changes in sleep pressure and its effects on cognitive function across acute sleep deprivation and recovery. Task 2 must include, at least, the following milestones:Month 10: Complete acquisition of biospecimens including collection of additional biological specimens/tissues during baseline, sleep deprivation, and recovery.o In additional cohorts of animals, obtain intestinal tissue, luminal fluid, or comparable specimens after baseline sleep and after sleep deprivation.o Obtain physiological measures associated with changes in sleep pressure due to sleep deprivation, and assess behavioral performance on cognitive tasks across acute sleep deprivation and recovery.Month 13: Analyze multiomic data from blood and fecal biospecimens from within-subjects cohorts (transcriptomics/metatranscriptomics, metagenomics, proteomics, and/or metabolomics) to identify molecules that arise from the gut microbiome/host interactions and correlate with changes in sleep pressure and its effect on cognitive function across acute sleep deprivation and following recovery sleep.o Complete multiomic analyses for all biospecimens.o From the multiomic dataset obtained from blood and feces biospecimens, complete the following data analyses to address changes in sleep pressure across acute sleep deprivation and recovery periods, as well as inter-individual variability in the effect of sleep pressure on cognitive task performance:. Calculate transcript relative abundance and fold change (= 2) in mRNA expression levels.. Assess phylogenetic diversity of the gut microbiome using Alpha diversity measures (Shannon H’ index of diversity, Simpson index of dominance, or similar) and Beta diversity (using Bray-Curtis dissimilarity measures). Determine relative abundance (% of the total sequences) of the bacterial genus level, and calculate fold difference. . Use Gene Ontology (GO) enrichment analysis to determine tissue-specific or ubiquitous gene functions, and to generate functional organized pathways/networks.. Identify microbiome derived biomolecules, perform functional interpretation using GO enrichment algorithms, and establish network mapping using pathway databases such as KEGG, Reactome, Ingenuity Pathway.Progress towards the stated goals will be assessed throughout the Base Period, with funding for Options 1 and 2 described below dependent on both funding availability and performance towards the Base Period milestones. Option 2 is also dependent on the government’s ability to provide multiomic datasets from human blood biospecimens obtained across varying degrees of sleep deprivation.Option 1: Multiomic data analysis to identify molecular pathways from the gut to the blood (13 MAC – 17 MAC): Using datasets generated in the Base Period – including additional biospecimens, such as luminal fluid and intestinal tissues, to augment datasets from blood and feces – perform systems-level analyses to identify correlated molecular events probabilistically associated with blood biomarkers of sleep pressure and its effects on cognitive task performance.Month 17: Complete analysis of multiomic datasets from additional biospecimens (e.g., intestinal tissue, luminal fluid, etc.) to validate correlations derived from analysis of blood and fecal biospecimens. Identify molecules that arise from interactions between the host and microbiome and correlate with changes in sleep pressure and its effect on cognitive function across acute sleep deprivation and recovery.Option 2: Correlation between human and animal blood biomarkers of fatigue (13 MAC - 17 MAC): Using a dataset of human blood samples collected prior to and throughout periods of acute sleep deprivation (to be provided by the government), along with the animal dataset collected in the Base Period, assess correspondence of molecular markers between the human and animal datasets with regard to their role in sleep/wake states and cognitive function in the context of acute sleep deprivation and recovery. The Option must include, at least, the following key milestones:Month 17: Using animal data collected in Base Period Task 1, along with human blood samples provided by DARPA, identify similarities and differences between humans and animals in relative concentrations of circulating biomolecules associated with sleep-wake states prior to and following acute sleep deprivation, as well as following recovery sleep.o Measure transcript relative abundance and calculate fold change (= 2) in expression mRNA expression levels in sleep deprived compared to non-sleep deprived individuals. Analyze specific immune related transcripts.o Identify biomolecules, perform functional interpretation using GO enrichment algorithms, and establish network mapping using pathway databases such as KEGG, Reactome, or Ingenuity Pathway.Ethical, Legal, and Societal Implications (ELSI): DARPA maintains its commitment to ensuring that efforts funded under this Special Notice adhere to ethical and legal regulations currently in place for Federal and DoD-funded research. Somnus developments will be discussed with a panel of expert external advisors with expertise in bioethical issues that may emerge as a consequence of advances in biomedical science and technology, including those that may occur beyond the scope of this Special Notice, such as modulation of the microbiome and/or sleep schedules in humans. Proposers should plan to support ELSI activities with DARPA, including semi-annual teleconference calls with an ELSI group that DARPA will engage. Somnus performers will need to consider the feedback from the ELSI group regarding their research activities, and to this end, ELSI outcomes will be reported regularly to DARPA.III. PROPOSAL ABSTRACT SUBMISSIONFor this special notice, DARPA strongly encourages that abstracts be submitted before any proposals. Please note that the deadlines for Somnus study abstract and proposal submissions are different from the general abstract and proposal deadlines that are listed in HR001122S0034. The abstract submission deadline for this special notice is April 17, 2023. Proposal abstracts must be submitted in accordance with the instructions in HR001122S0034 under Section 4, “Application and Submission Information.” Information on how to submit abstracts and proposals can be found on under section 4.2.4, “Submission Information,” in HR001122S0034. Proposal abstracts may not be submitted by fax or e-mail; any so sent will be disregarded.Teaming is encouraged to allow leveraging of the capabilities of different organizations, ultimately yielding an optimal structure to generate the most accurate and thorough identification of molecules or mechanisms associated with the restorative effect of sleep on cognitive performance. One contractor must be identified as the prime.BTO will respond to abstracts with a letter encouraging or discouraging the submission of a detailed full proposal containing technical and cost volumes. This recommendation will be based on the proposed effort’s relevance to the BTO mission and the Somnus study, a preliminary assessment of the scientific or technical merit, and interest in the technology concept. A DARPA Program Manager may contact you to further discuss the idea in your abstract. This procedure is intended to minimize unnecessary cost and effort in proposal preparation and review. The submission of an abstract, or a favorable review of an abstract, is not required prior to submitting a proposal.For abstracts that propose efforts that are considered of particular value to DARPA but either exceed available budgets or contain certain tasks or applications that are not desired, DARPA may suggest a full proposal with reduced effort to fit within expected available budgets.A favorable response to an abstract is not an assurance that a full proposal on the abstract’s topic will ultimately be selected for award.Abstracts must follow the same content guideline as described in Section 4.2.1, “Proposal Abstract Format,” in HR001122S0034. The cover sheet should be clearly marked “ABSTRACT for DARPA-SN-23-40,” and the total length should not exceed two (2) pages, excluding cover page, official transmittal letter, quad chart, and relevant appendices as outlined below. The page limitation for abstracts includes all figures, tables, and charts. No formal transmittal letter is required. All abstracts must be written in English.The 2-page body of the abstract should include the following:1. (Base) Description and rationale for paradigms and measurements designed to assess changes in physiology and cognitive function over the course of acute sleep deprivation and recovery sleep.2. (Base) Description and rationale for experimental testing with animal subjects to manipulate and measure sleep/wake states in the context of acute sleep deprivation and recovery.3. (Base) Description and rationale for experimental approaches to collect and analyze data on gut microbiota as well as gut-derived molecules and metabolites.4. (Base) Description and rationale for planned statistical analysis methods to identify gut microbiota, along with biomolecules and pathways derived from microbiome/host interactions, associated with sleep-deprived and non-sleep-deprived states, as well as with inter-individual differences in cognitive function across acute sleep deprivation and following recovery.5. (Option 1) Description and rationale for planned systems-level analyses of additional biospecimens, such as luminal fluid and intestinal tissues, to identify molecular pathways associated with blood biomarkers of sleep pressure and its effects on cognitive task performance.6. (Option 2) Description and rationale for analytical and statistical/computational approaches to identify correspondence of circulating metabolites associated with sleep-wake states and cognitive performance across acute sleep deprivation and following recovery between human and animal datasets.7. A plan to meet the proposed timeline.8. Risks and associated mitigation strategies.The Cover Sheet (does not count towards page limit) should include the administrative and technical points of contact (name, address, phone, fax, email, lead organization), the Special Notice number, title of the proposed project, primary subcontractors, estimated cost, and the label “ABSTRACT for DARPA-SN-23-40.”Abstracts not meeting the format described above and in HR001122S0034 will be considered non-conforming and will not be considered for review. DARPA intends to use electronic mail correspondence regarding DARPA-SN-23-40. All administrative correspondence and questions on this special notice, including requests for information on how to submit an abstract or full proposal to the BAA, should be submitted to the BAA Coordinator e-mail address: Somnus@darpa.mil.DARPA BTO encourages the use of the Federal Contract Opportunities website, http://www.SAM.gov, for retrieving HR001122S0034 and any other related information that may subsequently be provided.IV. FULL PROPOSAL SUBMISSION AND AWARDINFORMATIONThe full proposal submission date for this special notice (SN) is June 1, 2023. Full proposals received after that date may not be evaluated. Full proposals should be submitted in accordance with the instructions in HR001122S0034 under Section 4, “Application and Submission Information.” Proposals may not be submitted by fax or e-mail; any so sent will be disregarded. Guidance on the proposal format is provided under section 4.2.2, “Proposal Format.” It is encouraged, though not required, to use the statement of work (SOW) template provided as Attachment 1.Full proposals must include complete descriptions of the experimental approach for the Base Period and both option tasks that address the following:Base Period: Respondents must clearly describe and provide technical rationale for their proposed experimental approaches, animal model, cohort sizes, outcome measures, and statistical analyses for proposed experiments designed to induce acute sleep deprivation and measure sleep pressure and cognitive function. Rationale for these proposed approaches must address throughput, ease of implementation, probability of reliable outcome measures, statistical power, and future translatability to humans. Proposers must address potential challenges inherent to the proposed approaches, along with corresponding risk/mitigation strategies; in particular, respondents must also provide adequate justification for use of the proposed cognitive behavioral paradigms with animal subjects in a sleep-deprived state. Proposers must also describe how they will implement gold-standard methods for assessing sleep stages (e.g., polysomnography). Proposed approaches to develop new cognitive behavioral paradigms or new methods for sleep assessment are beyond the scope of this opportunity.Options:Option 1: Proposals must describe a plan to use datasets from additional tissues (e.g., luminal fluid, intestinal tissue, etc.) collected during experiments performed during the Base Period to establish probabilistic relationships between effects on the microbiome and blood across these tissue compartments. Multiomic analysis of these tissues should be complete by the end of the Base Period (Figure 1), and proposed work during this option should comprise analysis of these datasets.Option 2: Proposals must present a plan to assess a government furnished human dataset obtained from blood draws over an acute sleep deprivation protocol. These data should be analyzed in concert with the animal data collected during the Base Period of Somnus to identify similarities and differences between humans and animals in relative concentrations of circulating biomolecules associated with sleep-wake states prior to and following acute sleep deprivation, as well as following recovery sleep. Respondents are also encouraged to propose preliminary analyses to assess biomolecular correlates of cognitive outcomes of acute sleep deprivation across humans and animals, although it is not yet known whether the cohort size in the human dataset will be sufficiently large to assess the contribution of circulating biomolecules to inter-individual variability in cognitive performance measures following acute sleep deprivation.In accordance with HR001122S0034, proposals will be evaluated using the following criteria, listed in descending order of importance:(1) Overall Scientific and Technical Merit;(2) Potential Contribution and Relevance to the DARPA Mission;(3) Cost Realism;A detailed description of each evaluation criterion is provided in HR001122S0034.The amount of resources made available under this special notice will depend on the quality of the proposals received and the availability of funds. Although DARPA expects the above-described study to be executed, DARPA reserves the right to make changes.V. SIGNIFICANT DATES AND TIMESAbstract Submission Due DateApril 17, 20234:00 PM EDTFull Proposal Submission Due DateJune 1, 20234:00 PM EDTVI. POINTS OF CONTACTTechnical Point of Contact:Dr. Matthew Pava, DARPA/BTO, Somnus@darpa.mil.VII. WEBINARDARPA/BTO will hold a webinar on March 28, 2023 to provide critical information on the vision and objectives associated with the subject research opportunity. Participants must register to attend the Webinar through the registration website: https://events.sa-meetings.com/SomnusMar2023. Advance registration is required for every individual intending to view the Webinar, regardless of whether said individuals will be watching the webcast as a group. The Webinar URL will be provided once participants have registered. Webinar registration is limited to 500 remote participants. There is no fee for the Webinar. The Webinar will cover technical and cost proposal instructions. Therefore, both technical/scientific staff and administrative/contracting representatives from the office of sponsored research/programs are encouraged to attend.Registration Opens: As of publication of this announcement.Registration Closes: March 24, 2023 at 12:00 PM ET or when capacity is reached, whichever comes first.Interested attendees are invited to submit one (1) MS Power Point or Adobe PDF slide that summarizes their interests and capabilities, using the template provided (see Attachment 2) with this notice and on the registration website. These will be presented during 3-minute “lightning talks” at the Somnus Information Session. Submitted presentations consisting of multiple slides or a single slide with multiple layers will not be granted a time slot. Interested attendees must identify their intention to submit the lightning talk during registration. Due to limited availability, DARPA does not guarantee that these requests will be fulfilled. All presentations must be emailed to Somnus@darpa.mil no later than 12:00 PM ET on March 24, 2023.Interested parties are also invited to submit a one to two-page ‘teaming profile’ describing technical competencies, unique facilities and other capabilities, as they relate to the program, and desired technical/other competencies sought from other potential team partners. The profile must conform to the template provided with this notice and on the registration website and should include, at a minimum:• Contact information, to include name, organization, email, telephone number, mailing address, and website;• Brief description of the proposer’s technical competencies and relevant facilities;• Desired technical competencies and facilities from other potential team members, if applicable.All conforming teaming profiles must be emailed to Somnus@darpa.mil no later than 4:00 PM ET on March 31, 2023. Profiles that do not use the provided template (see Attachment 3) and/or exceed the two-page limit will not be accepted. Information contained in teaming profiles shall be publicly releasable – profile submitters consent to distribution amongst event registrants. After the webinar, teaming profiles will be sent via e-mail to all registrants on April 3, 2023. Specific content, communications, networking, and team formation are the sole responsibility of participants. Neither DARPA nor the DoD endorses any participating organization, nor does DARPA or DoD exercise any responsibility for improper dissemination of the teaming profiles.All administrative correspondence and questions on this Special Notice, including requests for information on how to submit an abstract or full proposal to the opportunity, should be submitted to the BAA Coordinator e-mail address: Somnus@darpa.mil. Answers to questions submitted in response to this special notice will be posted to the DARPA Opportunities Page, http://www.darpa.mil/work-with-us/opportunities, under the heading for the Biological Technologies Office. Submissions may not be submitted via fax or e-mail – any so sent will be disregarded.