Controlling Cellular Machinery Diagnostics and Therapeutics | Apply Online

Opportunity Summary:

DARPA's Defense Sciences Office issued this opportunity, titled "Controlling Cellular Machinery - Diagnostics and Therapeutics" (DARPA BAA 11-23), to push forward the science and engineering needed to build synthetic genetic regulatory elements that function reliably inside mammalian cells. The core aim is not incremental tuning of what already exists, but fundamental advances that make it possible to create, validate, and use modular genetic "building blocks" and circuits for real in vivo biomedical purposes, specifically to detect disease, treat it, or prevent it. In practice, DARPA is looking for proposals that move synthetic biology beyond proof-of-concept demonstrations and toward robust, predictable control of cellular behavior in the complex environment of mammalian tissues.

A central theme of the solicitation is the development of orthogonal and modular regulatory components. "Orthogonal" here means the engineered regulatory parts should operate independently from the host cell's native pathways as much as possible, rather than cross-talking with normal cellular regulation in ways that cause unintended side effects or performance drift. "Modular" means these parts should be composable, so researchers can assemble them into larger genetic programs without having to re-engineer everything each time. The solicitation emphasizes that these modules must be stable and functional in the cellular environment, maintain independent function without interference for long enough to achieve the desired clinical effect, and limit their interactions with cellular metabolism or the surrounding milieu to what is necessary for the intended performance characteristics.

DARPA highlights several technical challenges that proposed work should address. These include discovering new regulatory elements, characterizing how they behave in mammalian cells, and applying evolution or rational design methods to create improved or entirely new control elements. Beyond the parts themselves, the program is interested in demonstrating integrated genetic circuits that can be synthesized, amplified, and delivered into mammalian cells. That means proposals need to grapple with the full pipeline from circuit design to practical implementation, including how to get novel circuits into cells and have them perform as intended under biologically realistic conditions, rather than only in simplified laboratory settings.

The biomedical scope is explicitly focused on diagnostics and therapeutics, meaning engineered cellular systems that can sense disease-relevant signals, compute or make decisions based on those signals, and trigger an appropriate response such as releasing a therapeutic molecule, switching a pathway on or off, or otherwise altering cellular function to achieve a clinical benefit. At the same time, DARPA draws a clear boundary around what it does not want: research that mainly delivers evolutionary, incremental improvements to the existing state of practice is specifically excluded. In other words, proposals should present approaches that represent a meaningful leap in capability, generalizability, or reliability, rather than modest optimization of known tools.

The funding mechanism listed for this announcement includes cooperative agreements and procurement contracts, and there is no cost-sharing or matching requirement. Eligibility is broadly open (unrestricted) to any type of entity, subject to any clarifications contained in the full announcement. The opportunity was posted on November 29, 2010, with an original and current closing date of March 3, 2011, and an archive date of May 3, 2011. It is categorized under science and technology and other research and development, with CFDA number 12.910, which corresponds to Department of Defense research and technology development activities.

Finally, DARPA notes an important carve-out for teams interested in vaccine applications. If a proposer intends to pursue nucleic acid vaccines as the application area, DARPA directs them to a companion solicitation, "Controlling Cellular Machinery - Vaccines" (DARPA BAA 11-22), rather than this diagnostics and therapeutics announcement. The listed point of contact for access issues with the full announcement is Dr. Daniel Wattendorf, the BAA Coordinator.

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