Our solution comprises a five-layer stack as illustrated in the figure on the right. Using the Clotho
platform, we develop two applications for specifying and executing
biological protocols. The Assembly Planner is the end-point of an
end-to-end design workflow that produces an assembly plan for synthetic
biological devices, with each assembly step annotated with the name of a biological protocol. Each
such protocol itself may be fully specified using another Clotho application called PuppetShow, which
provides an environment for writing, testing, debugging, and executing biological protocols.
The protocols are written in a new python-based high-level language called Puppeteer. The Language layer
comprises the Puppeteer interpreter and linker. A protocol specified in Puppeteer may contain
Puppeteer instructions as well as references to previously created Puppeteer programs available in a
library. The Language layer expands and translates a Puppeteer protocol to a sequence of low-level
commands expressed in a Common Human Robot Instruction Set (CHRIS). CHRIS provides a standardized
instruction set that high level biological protocol languages like Puppeteer may assume to be
supported by any robot. Any high-level language may produce CHRIS programs and any robot vendor may
support a superset of CHRIS: this decouples robot hardware details from biological protocol and
specification details and supports our goal of portability and protocol library reuse. The Hardware
Layer---the external control and I/O interface of a robot---is wrapped under a Hardware Abstraction
Layer (HAL). Vendor-provided software for programming the robot may be proprietary and is used to
control the robot. An interface to it is provided by a software bridge, which maps protocols
expressed in CHRIS to sequences of native robot instructions.
The Resource Management layer maintains resource state information and provides a standardizable
high-level interface for initializing, requesting, naming, aggregating, and accessing resources to
the Language layer, analogous to a ``system call'' suite. This interface supports our goal of
removing the minutiae of resource management from the protocol specification language.
Results:
We have finished implementation of an initial version of the Puppeteer stack; it is fully integrated with the Clotho platform. We have implemented basic BioBricks assembly protocols and validated them in the wet lab by assembling basic devices.
Collaboration with other iGEM teams:
In order to ensure reproducibility and promote collaboration, we visited Jonathan’s lab at MIT to set up PuppetShow on their robot. We met a few of MIT’s iGem team members and coordinated with Jonathan to test the Puppeteer flow on the MIT robot. During this process, we noticed some differences between our robot deck setups that made PuppetShow incompatible with MIT’s deck unless some parameters and settings were soft-coded. We then proceeded ensure Puppeteer is more portable. After making these improvements, we successfully tested the Puppeteer flow on the MIT deck and everything ran as expected. This collaborative effort with MIT’s iGem team is definitely fruitful because it made PuppetShow more robust and ensured functionality across multiple robots.
Future Work:
Integration between Puppeteer/Puppetshow and the eLabNotebook is planned for implementation.
Ethical User Study practices:
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Overview: PuppetShow
Constructing a combinatorial library of devices is tedious using manual laboratory techniques and would require hundreds of hours of careful work. To remedy this, we are implementing the Puppeteer Biological Protocol
Automation Suite. This suite includes a high level programming language for specifying biological
protocols commonly used in the laboratory, which are then executed by a liquid-handling robot with
minimal user intervention.
Demo Video
Wetlab
We implemented two protocols central to BioBricks assembly---Restriction Digestion and Ligation---in Puppeteer. We validated the Puppeteer implementation by executing multiple trials of both protocols and verifying the result by running a gel.
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