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Rhodium DARPA Biomanufacturing 01

Efficient and Resilient Biomanufacturing in Variable Gravity
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Efficient and Resilient Biomanufacturing in Variable Gravity (Rhodium DARPA Biomanufacturing 01) characterizes the effect of different levels of gravity on the production of therapeutics and nutraceuticals from bacteria and yeast. Prior spaceflight studies show that microgravity causes changes in microbe cell growth, cell morphology, and metabolic activity that affect biomanufacturing performance. Results could inform strategies to improve biomanufacturing in space and provide for humans on future missions.

The following content was provided by Olivia Holzhaus, and is maintained by the ISS Research Integration Office.

Experiment Description

Research Overview

  • Using microbes to make goods such as biopolymers, food, and pharmaceuticals in space has been theorized as a possible approach to reduce the substantial economic and energy costs required to transport equipment and consumables from Earth into space and is a potentially less expensive approach than traditional chemical and mechanical techniques.
  • The practical viability of space biomanufacturing is an open problem because spaceflight imposes numerous physiological stresses on microbes, affecting growth rates, output responses, and thus potential productivity and scalability; one such stress is a reduced gravity level compared to Earth.
  • Efficient and Resilient Biomanufacturing in Variable Gravity (Rhodium DARPA Biomanufacturing 01) establishes how biomanufacturing a suite of useful therapeutics and nutraceuticals in the space environment may be possible by using different bacteria and yeast species at three gravity levels: micro, Lunar, and Martian.
  • Data collected will help inform future testing parameters and provide proof of concept for the feasibility of in-orbit servicing, assembly, and the manufacturing of U.S. assets in space.

Description

Biomanufacturing is the process of using living systems such as microorganisms and cell cultures to produce materials and biomolecules on a commercial scale. Efficient and Resilient Biomanufacturing in Variable Gravity (Rhodium DARPA Biomanufacturing 01) is an investigation funded by the Department of Defense (DoD) and the Defense Advanced Research Projects Agency (DARPA) to determine whether biomanufacturing is feasible in a microgravity environment.

In theory, space biomanufacturing can substantially reduce mission costs. However, the practical viability of space biomanufacturing is an open problem because spaceflight imposes numerous physiological stresses on microbes, which impacts growth rates, transcriptional and translational responses, and ultimately potential biomanufacturing output and scale.

To better understand the impact that different levels of gravity have on the potential output and scale of biomanufacturing setups, this investigation answers fundamental questions about future space biomanufacturing feasibility by quantifying current biomanufacturing performance in space. This quantification is an important step to accomplishing the investigation goal: to optimally biomanufacture a suite of useful therapeutics and nutraceuticals in the space environment using different bacteria and yeast species in a way that is resistant to changes across a gravity continuum. “Optimally” is here defined with respect to (1) efficiency – biomanufacturing productivity (yield and titer) compared to anticipated costs (launch and/or operational mass/volume/power/logistics), and (2) resiliency – performance constancy that endures despite harsh, uncertain, and variable space environment conditions, and in particular, different levels of gravity.

The key barrier to efficient and resilient space biomanufacturing is that some microbes exhibit differential gene expression in fractions of Earth-gravity relative to Earth-based controls. Microgravity alters microbial gene expression, leading to changes in cell growth, cell morphology including biofilm formation, pathogenicity, and metabolic activity. But the response of microbes to microgravity changes is highly dependent on the taxa. Additionally, an organism’s responses to simulated microgravity vary widely with the type of simulation apparatus used, which means that bioengineering to improve biomanufacturing performance that has been tested in this simulation apparatus may be suspect. Further, there are several studies that show a lack of reproducibility of simulated transcriptional responses in actual spaceflight. Even widely tested Escherichia coli might behave very differently in test apparatus compared to published modeled microgravity and spaceflight experiments under different hardware and environmental conditions.

Therefore, this investigation includes testing several practical biomanufacturing microbes and useful product molecules in spaceflight conditions. Results are expected to increase the understanding of space biomanufacturing function across a gravity continuum. Outcomes should enable researchers to contrast biomanufacturing behaviors under different gravity conditions with outcomes generated on Earth that are currently used to predict on-orbit molecule production.

Biomanufacturing efficiency is attained through data-driven modeling and quantitative analysis of the effects of low gravity as shown by collected spaceflight data to ascertain feasible growth rate and titer performance targets. Potential functionality losses in space are quantified from the obtained data and merged with any previously collected or existing organism flight data that may be limited, noisy, or not focused on biomanufacturing. Optimally efficient strategies for environment and host conditioning are articulated from all data. Such strategies may, in the future, be tested in terrestrial analogs that replicate space biomanufacturing performance.

The objectives of this investigation are:

1. To supplement preliminary baseline characterizations of biomanufacturing performance.

2. To expand the set of identified genetic regulation targets when biomanufacturing in low gravity.

3. To update predictive computational models and physical analogs of biomanufacturing performance across a gravity continuum.

The research outcomes of this investigation increase understanding of the feasibility of biomanufacturing beyond Earth, sustain U.S. technological superiority, and enable the development of a robust space supply chain.

Applications

Space Applications

Producing biopolymers, food, and pharmaceuticals from microbes could reduce the economic and energy costs of transporting equipment and consumables from Earth on long-duration missions such as to the Moon and Mars. Results from this investigation could provide a better understanding of how spaceflight affects microbial biomanufacturing and lead to strategies to improve its performance on future missions.

Earth Applications

Environmental stressors can reduce the output of microbe biomanufacturing. By providing a better understanding of how these microbes adapt and function in the stresses of the space environment, this investigation could support development of measures to maintain and enhance biomanufacturing output in stressful environments on Earth.

Operations

Operational Requirements and Protocols

Rhodium DARPA Biomanufacturing 01 requires the launch of the Rhodium Variable Gravity Simulator 01, six Rhodium Science Chamber 1LIV units, and the Rhodium Science TempLog 20iB. The Rhodium Variable Gravity Simulator 01 provides the capacity to test biological samples in multiple gravitational force environments, including Lunar and Martian gravity. The Rhodium Science Chamber 1LIV chamber is integrated into the Rhodium Variable Gravity Simulator 01 and provides sufficient culturing volumes for multiple sample replicates. Chambers are frozen from hardware turnover through ascent.

After arrival at the International Space Station, the chambers are transferred into onboard cold stowage assets during visiting vehicle unpacking operations. Chambers remain frozen until investigation activation. The chambers are then thawed, incorporated into the Rhodium Variable Gravity Simulator 01, and incubated at set gravitational forces and for designated lengths of time to provide ample growth of the microbial cells. During incubation, the Rhodium Science TempLog 20iB monitors environmental temperature. At the completion of each designated incubation time, a chamber is transferred back to a freezer for the remainder of the mission. The next chamber is then loaded into the Rhodium Variable Gravity Simulator 01 for incubation at the new gravity setting and for the new incubation time. This operation sequence is repeated for all six chambers. The chambers remain frozen during the remaining time on orbit, through descent and delivery to the research team’s laboratory.

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