[Plsfaculty] FW: [Faculty] DARPA in microphysiological systems

[Brian Larkins]

Dean Burgess asked that this be sent to CALS faculty.

 

From: Paul Cohen [mailto:cohen at sista.arizona.edu] 
Sent: Saturday, September 17, 2011 1:05 PM
To: Giovanni - (gbosco) Bosco; Ian Fasel; Kobus Barnard; Clayton Morrison;
Shane Burgess; Nirav Merchant; Joaquin Ruiz; Paul Cohen
Subject: DARPA in microphysiological systems

 

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:

 

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.

 

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:

 

CHIP MEDICINE: 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 ScienceInsider
<http://capitalengineer.cmail1.com/t/y/l/skkjlk/bpktjijk/k/> . DARPA will
work on the engineering, and is soliciting proposals
<http://capitalengineer.cmail1.com/t/y/l/skkjlk/bpktjijk/u/> . The White
House <http://capitalengineer.cmail1.com/t/y/l/skkjlk/bpktjijk/o/>  is
enthusiastic. 

 

More excerpts from the DARPA BAA
<https://www.fbo.gov/index?s=opportunity&mode=form&id=d12e2f420cb12f75d61a86
82623c3a79&tab=core&_cview=1> , below.

 

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. 

 

Thanks, --Paul

 

 

 

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.

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.

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:

 

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.

 

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.

 

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.

 

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.

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.

 

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

 

In addition to the four technical areas described above, proposers have the
option of addressing one additional technical area, Disease Models.

 

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

appropriate level of safety. Proposals that do not address this technical
area will not be penalized.

 

 

______________________________

Paul Cohen

Professor and Director, 

School of Information: Science, Technology and Arts

University of Arizona

520 626 2818

www.sista.arizona.edu/~cohen

calendar at http://tinyurl.com/prccalendar

 

Assistant:  

Lupe Jacobo, 520 626 0510

ljacobo at email.arizona.edu 

______________________________

 

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