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</o:shapelayout></xml><![endif]--></head><body lang=EN-US link=blue vlink=purple><div class=WordSection1><p class=MsoNormal><span style='font-size:11.0pt;font-family:"Calibri","sans-serif";color:#1F497D'>Dean Burgess asked that this be sent to CALS faculty.<o:p></o:p></span></p><p class=MsoNormal><span style='font-size:11.0pt;font-family:"Calibri","sans-serif";color:#1F497D'><o:p> </o:p></span></p><div><div style='border:none;border-top:solid #B5C4DF 1.0pt;padding:3.0pt 0in 0in 0in'><p class=MsoNormal><b><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif"'>From:</span></b><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif"'> Paul Cohen <a href="mailto:[mailto:cohen@sista.arizona.edu]">[mailto:cohen@sista.arizona.edu]</a> <br><b>Sent:</b> Saturday, September 17, 2011 1:05 PM<br><b>To:</b> Giovanni - (gbosco) Bosco; Ian Fasel; Kobus Barnard; Clayton Morrison; Shane Burgess; Nirav Merchant; Joaquin Ruiz; Paul Cohen<br><b>Subject:</b> DARPA in microphysiological systems<o:p></o:p></span></p></div></div><p class=MsoNormal><o:p> </o:p></p><div><p class=MsoNormal>Folks, this is potentially a big deal for us. DARPA has teamed up with FDA to develop technology for fast drug discovery and screening. They had a workshop earlier in the summer and now have released a BAA with multiple awards anticipated. The one sentence description is:<o:p></o:p></p></div><div><p class=MsoNormal><o:p> </o:p></p></div><div><div><p class=MsoNormal><span style='font-size:9.0pt'>DARPA seeks an in vitro platform of human tissues that accurately predicts the safety, efficacy, and pharmacokinetics of drugs and vaccines before their administration to humans.<o:p></o:p></span></p></div></div><div><p class=MsoNormal><o:p> </o:p></p></div><div><p class=MsoNormal>To me, "predicts" is a key word and suggests that a team of biologists and machine learning people might mount a successful bid. The other key word is "platform," according to CapitolShorts:<o:p></o:p></p></div><div><p class=MsoNormal><o:p> </o:p></p></div><blockquote style='margin-left:30.0pt;margin-top:5.0pt;margin-right:0in;margin-bottom:5.0pt'><div><p class=MsoNormal><span class=apple-style-span><b>CHIP MEDICINE:</b> DARPA and the new National Institutes of Health translational sciences center are teaming up to develop a chip that would allow more efficient drug screening. The $140 million, five-year project aims to combine human cells in ways that lets them "talk to each other" and model how a drug would affect human tissue, according to <a href="http://capitalengineer.cmail1.com/t/y/l/skkjlk/bpktjijk/k/">ScienceInsider</a>. DARPA will work on the engineering, and is soliciting <a href="http://capitalengineer.cmail1.com/t/y/l/skkjlk/bpktjijk/u/">proposals</a>. The <a href="http://capitalengineer.cmail1.com/t/y/l/skkjlk/bpktjijk/o/">White House</a> is enthusiastic. </span><o:p></o:p></p></div></blockquote><div><p class=MsoNormal><o:p> </o:p></p></div><div><p class=MsoNormal>More excerpts from the DARPA <a href="https://www.fbo.gov/index?s=opportunity&mode=form&id=d12e2f420cb12f75d61a8682623c3a79&tab=core&_cview=1">BAA</a>, below.<o:p></o:p></p></div><div><p class=MsoNormal><o:p> </o:p></p></div><div><p class=MsoNormal>Whitepapers are due Oct. 27, full proposals Dec. 12. Please let me know very soon who should be on the team, and I will call a meeting to kick off the effort. <o:p></o:p></p></div><div><p class=MsoNormal><o:p> </o:p></p></div><div><p class=MsoNormal>Thanks, --Paul<o:p></o:p></p></div><div><p class=MsoNormal><o:p> </o:p></p></div><div><p class=MsoNormal><o:p> </o:p></p></div><div><p class=MsoNormal><o:p> </o:p></p></div><div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>DARPA is soliciting innovative research proposals to develop an in vitro platform of engineered tissue constructs that reproduces the interactions that drugs or vaccines have with human physiological systems. The tissue constructs must be of human origin and engineered in such a way as to reproduce the functions of specific organs and physiological systems. All of the following physiological systems must be functionally represented on the platform by the end of the program: circulatory, endocrine, gastrointestinal, immune, integumentary, musculoskeletal, nervous, reproductive, respiratory, and urinary.</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>5DARPA envisions a platform that is flexible, reliable, and accessible to the scientific community at reasonable cost. Proposers are expected to manage intellectual property (IP) rights such that transition of the platform and methods to the scientific community is achieved to the greatest extent possible.</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>DARPA anticipates that the Microphysiological Systems program will provide up to five years of funding for research and development, divided into a base period of no more than 18 months followed by three additional periods of up to 14 months each. Proposers must present a plan for developing a platform and integrated tissue constructs that recapitulate all ten physiological systems listed above. Proposals must address the following four technical areas, and may also address an optional fifth technical area:</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:9.0pt'><o:p> </o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>1. Platform engineering DARPA envisions a reconfigurable platform that permits the simultaneous study of ten or more in vitro physiological systems, arranged in any sequence. The platform should allow the experimenter to monitor and maintain the viabilities of the resident tissues for up to four weeks. Designs that are flexible, user-friendly and reliable are preferred, as are designs that permit the biological components to interact in a physiologically relevant manner. Design considerations consistent with the transition plan (see below) should be identified and taken into account throughout the development cycle. Platforms must also be designed, built, and demonstrate sufficient functional or reserve capacity such that the total tissue sustained by the end of the Base period (and each additional Period) is equivalent to the full complement of ten physiological systems expected at the end of the program. Depending on the number of different physiological systems available at the time (see Milestones below), multiple copies of one or more systems should be used so that ten systems are sustained by the platform at the end of each funding period.</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:9.0pt'><o:p> </o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>2. Physiological systems Proposers should describe their plan for developing engineered tissue constructs that mimic the listed physiological systems. These constructs must reproduce the interactions that normally occur among the components of each physiological system as well as the interactions with drug/vaccine candidates. The constructs may correspond to individual tissues and organs or they may be comprised of multiple cell types arranged to reproduce the functionality of a physiological system. Regardless of the architecture, performers are expected to demonstrate that their constructs reproduce authentic and characteristic responses of each physiological system. Barrier and depot tissues that typically affect drug or vaccine pharmacokinetics should also be considered for incorporation into the platform. The engineered constructs must be made of cells of human origin. Transformed cells are acceptable only if no alternatives exist and convincing justification is provided in the proposal. Preference will be given to proposals that will utilize commercially available human cells by the end of the program. Proposers must describe the measurements, tests, and assays they will use to assess the viabilities and functions of the constructs as they are exposed to candidate drugs/vaccines.</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:9.0pt'><o:p> </o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>3. System integration Proposers should describe their plan for integrating the individual physiological system constructs and platform such that the physiological systems retain their viability and interact with others in a physiologically relevant manner for up to four weeks. The order in which the individual systems are developed and integrated is up to the proposer. The number of integrated physiological systems is dictated by the program milestones given below, with the expectation that all ten physiological systems will be represented on the platform at the end of the program.</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:9.0pt'><o:p> </o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>4. Prediction and validation Proposers should describe their modeling and/or computational methods for extrapolating data obtained from the platform to intact humans. The specific assays, measurements, and data that will be used should be described in the proposal. It is not required that these be integrated into the platform, only that the platform is compatible with the chosen measurements or assays. Performers will be expected to show that pharmacokinetic parameters for test compounds estimated from platform- derived data correspond to the known values in humans. This characterization should include, but is not limited to, drug/vaccine time course and half-lives, clearance, tissue distribution, and metabolic and elimination pathways. Barrier and depot tissues that typically affect drug or vaccine pharmacokinetics should also be considered for incorporation into the platform.</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>Proposers should present a detailed plan for validating integrated platform performance. At the end of each period of performance, performers are expected to estimate the efficacy, toxicity, and pharmacokinetics of one or more drugs/vaccines that have already been administered to humans. Proposers should choose test compounds from each of the four categories listed below based on published clinical studies. These choices should also be relevant to the physiological systems resident on the platform at the time of testing and should include at least one test compound that was thought to be safe on the basis of preclinical testing but later found to be toxic in humans.</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:9.0pt'><o:p> </o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>i. Drugs/vaccines known to be safe and effective ii. Drugs/vaccines known to be safe and ineffective iii. Drugs/vaccines known to be unsafe, but effective iv. Drugs/vaccines known to be unsafe and ineffective</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:9.0pt'><o:p> </o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>In addition to the four technical areas described above, proposers have the option of addressing one additional technical area, Disease Models.</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:9.0pt'><o:p> </o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>5. Disease Models (optional) Proposers have the option to describe plans for establishing an in vitro infectious disease model. Performers will be expected to show that the infectious agent will infect the in vitro platform and that biomarkers normally associated with infections in humans are present. The safety, efficacy, and pharmacokinetics of known countermeasures to the infection should be estimated and compared to estimates derived from intact humans, if known. It is anticipated that research in this technical area will begin after the base period has been completed and will be conducted at an</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:10.5pt'>appropriate level of safety. Proposals that do not address this technical area will not be penalized</span></span><span style='font-size:9.0pt'>.<o:p></o:p></span></p></div></div><div><p class=MsoNormal><o:p> </o:p></p></div><p class=MsoNormal><o:p> </o:p></p><div><div><div><p class=MsoNormal><span style='font-size:10.0pt;font-family:"Verdana","sans-serif";color:navy'>______________________________</span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:10.0pt;font-family:"Verdana","sans-serif";color:navy'>Paul Cohen</span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:10.0pt;font-family:"Verdana","sans-serif";color:navy'>Professor and </span><span class=apple-style-span><span style='font-family:"Verdana","sans-serif";color:navy'>Director, </span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-family:"Verdana","sans-serif";color:navy'>School of Information: Science, Technology and Arts</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:10.0pt;font-family:"Verdana","sans-serif";color:navy'>University of Arizona</span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:10.0pt;font-family:"Verdana","sans-serif";color:navy'>520 626 2818</span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:10.0pt;font-family:"Verdana","sans-serif";color:navy'><a href="http://www.sista.arizona.edu/~cohen">www.sista.arizona.edu/~cohen</a></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:10.0pt;font-family:"Verdana","sans-serif";color:navy'>calendar at </span><span class=apple-style-span><span style='font-size:7.5pt;font-family:"Helvetica","sans-serif";color:#00984E'><a href="http://tinyurl.com/prccalendar">http://tinyurl.com/prccalendar</a></span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:9.0pt'><o:p> </o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:7.5pt;font-family:"Verdana","sans-serif";color:navy'>Assistant: </span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:7.5pt;font-family:"Verdana","sans-serif";color:navy'>Lupe Jacobo, 520 626 0510</span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span class=apple-style-span><span style='font-size:7.5pt;font-family:"Verdana","sans-serif";color:navy'><a href="mailto:ljacobo@email.arizona.edu">ljacobo@email.arizona.edu</a> </span></span><span style='font-size:9.0pt'><o:p></o:p></span></p></div><div><p class=MsoNormal><span style='font-size:10.0pt;font-family:"Verdana","sans-serif";color:navy'>______________________________</span><span style='font-size:9.0pt'><o:p></o:p></span></p></div></div></div><p class=MsoNormal><o:p> </o:p></p></div></body></html>