Pharmaceutical foundry considerations will also need to include medical risk and patient outcomes

Developing detailed spatial below-ground information about both plant and microbial location was considered to be both a priority and a major hurdle by many attendees.Current approaches include infrared, X-ray, chemical sensing, and acoustic imaging although all have limitations.The EcoPOD provides an opportunity to collaborate with teams who are developing these methods, such as those at the Danforth Center and the ARPA-E TERRA program, to test existing methods over a range of soil types and conditions such as temperature and soil saturation, as well as develop new methods.The EcoPOD user has access to the full depth of the soil column.This gives an opportunity to place sensors through the column.Many sensors exist, but may benefit from miniaturization, as space is still relatively limited in the EcoPOD quadrants.This is a good opportunity to develop collaborations with both academia and industry partners for the engineering expertise needed to miniaturize sensors.The group noted that above ground phenotyping and sensing is relatively advanced, primarily due to the physical ease of access.As a result, there are many more field derived datasets to compare to experiments performed in the EcoPOD.This will be useful for bench marking.In particular, multiple participants raised concerns about whether the artificial lighting was sufficient.Previous Ecotron efforts have often been criticized for the poor quality lighting but recent advances in LED lighting may resolve much of this and the EcoFAB team has recently found that they can simulate field lighting conditions using new PHYTOFY RL LED lights which are tunable in 6 different spectra from UVA to far red that could also be used in EcoPODs.Collecting sensor and imaging data on aerial growth of plants under a set of standard conditions in a defined field soil should be a priority.

There has been much recent interest in predictive phenotyping, where data on young plants is predictive of mature traits such as yield and grain quality.This has been developed in field systems,ebb and flow trays including via Advanced Research Projects Agency–Energy funded projects such as Transportation Energy Resources from Renewable Agriculture , but the EcoPOD would allow further interrogation of these models, in particular the response to individual climatic parameters e.g., drought vs.temperature.The addition of EcoPOD capabilities to bridge the gap between small-scale EcoPOD and large scale field capabilities will enable scientists to address critical DOE missions in energy and the environment.For example these capabilities will enable elucidation of molecular mechanisms by which microbial communities and abiotic constraints control key geochemical processes such as soil carbon cycling.They will also enable rapid development and translation of beneficial microbial communities from benchtop to field applications to support efforts in sustainable bio-energy and bio-products.Importantly, the containment and control afforded by EcoPODs and EcoFABs will enable pioneering studies in secure bio-systems design to provide key insights into the persistence, fate, and control of engineered microorganisms within soil micro-environments.Finally, there are opportunities to collaborate with other fabricated ecosystem projects at various scales across the globe.There was a lot of enthusiasm from the participants about using the EcoPODs for experiments that are challenging to do in the field due to regulatory or safety concerns.Examples include understanding the persistence and fate of engineered microbes within contained and controlled environments to identify risks and effective containment strategies.It was also noted that it’s an opportunity to monitor the effects of potentially environmentally hazardous materials such as plastic microfibers or carbon nanotubes.There was also interest from National Labs with secure facilities who could adapt technologies such as the EcoBOT, a robot that enables automated EcoFAB experiments, and EcoPOD, once they are derisked and developed further, for work which requires secure facilities that are not available at Berkeley Lab.

Due to the breadth of scientific background among our workshop participants, many great experimental ideas were discussed including topics such as carbon sequestration experiments, for which the EcoPOD’s semi-closed system can facilitate mass balance calculations easier than in field experiments.Furthermore, deep soil processes were discussed as most data from soil experiments does not exceed the top 10 cm.Additionally, soil atmosphere gas exchange was mentioned, which we will keep in mind as we are aiming to develop future prototypes that can provide gas-tight conditions.Similarly, climate change simulations that include warming or elevated CO2 concentrations are a future experimental goal that will require prototype updates that are achievable.All participants were excited about the possibility of separating individual environmental parameters to observe their effect on the plant-microbe-soil atmosphere ecosystem.This includes being able to better predict the phenotype of engineered bio-energy crops under different environmental conditions, reducing the need for expensive and complex multi-site field trials.The EcoFAB team has made access to the units purchased by Berkeley Lab a priority.For example, detailed protocols on how to fabricate them have been published , and TEAMS, a project funded by DOE, is dedicated towards the dissemination of EcoFAB supplies and protocols including model micro-biomes to foster interlaboratory science and experimental standards.Through these efforts, laboratories across the globe are now using Berkeley Lab-designed EcoFABs as well as developing their own iterations, with a new EcoFAB ring-trial study with B.distachyon and a synthetic microbial community planned for early 2021.As discussed above, EcoFABs and EcoPODs are complementary technologies with different strengths and weaknesses.One way Berkeley Lab is leveraging this fact is through the use of higher throughput EcoFABs experiments to assess important parameters that can later be implemented within EcoPODs.

The EcoBOT being developed at Berkeley Lab through the Trial Ecosystems for the Advancement of Microbiome Science project will support remote, high throughput EcoFAB experiments to improve to improve turnaround, standardization, and reproducibility for EcoFAB experiments.ESM analyses are typically performed to evaluate and optimize space mission payloads to minimize launch costs as a function of mass, volume, power, cooling, and crew time needs.NASA’s exploration medical system trade study tools, which includes a systems engineering model and a medical risk analysis model, have the potential to serve as a foundation for this analysis.There are many obstacles ahead before making pharmaceutical foundries in space a reality.What has not been thoroughly discussed in this review is the downstream processing of a molecular medical foundry, which will depend on the purity needed for the pharmaceutical formulation, delivery method, production host, etc.Downstream processing, the purification of the target molecule from the production host, is a resource-intensive aspect of bio-pharmaceutical production across all platforms.There is a lack of downstream processing technology that translates well from Earth-based constraints to those of space, as they often require a high quantity of consumables, raw materials, equipment, and cleaning.This bottleneck will need to be addressed for pharmaceutical foundries in space to succeed.One approach is to conduct research on novel drug delivery modalities to reduce the need for downstream processing, and another is to diminish the resource demands of the processing itself.A growing emphasis on distributed and just-in-time pharmaceutical production for healthcare on Earth is already driving solutions to these downstream challenges.The other major hurdle is in regulatory compliance.Production and administration of pharmaceuticals in space will require extensive quality control; manufacturing a small molecule might have 50 critical tests, while manufacturing a biologic may have over 250 tests.Here, the advent of personalized medicine on Earth will illuminate a path forward.The shift from mass produced to individualized patient-specific medicine hinges on re-structuring the path to regulatory approval and quality control.While there are many challenges ahead that need to be addressed to pave the way for Earth-independent life support, the rewards of this pursuit will include great insights into supporting life on Earth and beyond.Understanding this value, we aim to highlight the critical importance of developing Earth-independent systems in the future of human exploration.We illustrate that molecular pharming provides a diverse production tool set that could be used to establish a robust molecular medical foundry subsisting on a small fraction of food crop needs.In addition to advocating for molecular pharming as a synergistic asset of space life support systems,4×8 flood tray we focus on the need for multi-faceted utilization of resources in limited environments such as space and extraterrestrial bodies.Sunflower is an oil seed crop of great importance worldwide, due to the excellent quality of the oil extracted from its seeds that are consumed in various ways.Cultivation of the sunflower is becoming increasingly significant globally.In 2008–2009, the world sunflower seed production was about 33 million tones, around 8.5% of the world’s total oil seed production , the leading producers of which are the EU, Russia, Ukraine, Argentina, USA,China, India, and Turkey.Foliar fertilization is an increasingly popular practice with particular importance for the production of high value crops such as sunflowers with many examples of positive responses to foliar application of micro-nutrients, including zinc , iron ,boron , manganese , and molybdenum , on the seed yield and seed quality of sunflower.Foliar fertilization has particular value in overcoming nutrient deficit resulting from stress conditions, such as salinity and drought, which often compromise root growth and decrease root absorption capacity.Foliar application of Zn resulted in a greater improvement in Zn densities in rice and wheat grain when compared with soil applied Zn.

Foliar fertilization is theoretically more immediate and target oriented than soil fertilization since nutrients can be directly delivered to plant.Thissues during critical stages of plant growth.Optimizing the efficacy of the foliar applied nutrients is therefore of great importance from an economic, agronomic and environmental point of view.Our understanding of the factors that determine the ultimate efficacy of foliar applications remains poor and the response of plants to foliar Zn applications is highly variable.Many reports indicate that foliar application of Zn may significantly increase the concentrations of Zn in the applied leaves but may have little effect on foliar concentrations in non-sprayed Thissues or Thissue that develop subsequent to the foliar application.The factors that control the uptake and subsequent translocation of foliar applied nutrients out of the leaf, and the effect of spray formulation on these processes are poorly understood.While various approaches have been used to determine the efficacy of foliar applied nutrients using stable and radioactive isotopic labeling , it remains challenging to determine the pathways of mobilization from leaf to shoot and to monitor the influence of foliar formulation on phloem loading and micro-nutrient transport.To address the inherently low efficiency of many foliar Zn formulations, a wide range of commercial products have been developed and marketed.Recently, there has been much interest in the incorporation of organic moleculesor bio-stimulants into foliar fertilizers with the rationalization that these additives will enhance the uptake, or subsequent mobility of the applied nutrient.The term ‘bio-stimulant’ is used to describe a substance or material, with the exception of nutrients and pesticides, which when applied to plants has the capacity to beneficially modify plant growth.Currently there is very little scientific evidence that bio-stimulants can specifically enhance the uptake and utilization of foliar applied fertilizer materials.The technique of X-ray fluorescencehas been widely used in the research of elemental distribution in plant Thissues, and has proved to be a promising tool to study in vivo localization of metals in plants due to its high-resolution and sensitivity.XRF analyses can be performed to visualize cellular and subcellular distribution of elements in plants without significant pretreatment of the samples.We have previously applied this technique to characterize the location and to monitor changes in concentration and distribution of Zn during plant development or following foliar applications.In this current study, we will utilize μ- XRF to obtain high spatial quantification of elemental distribution and transport following the application of various Zn formulations with the aim of:increasing our understanding of the processes that govern the localization and transport of foliar applied nutrients with emphasis on Zn, and to determine if the formulation of the foliar applied Zn, with addition of macro-nutrients or bio-stimulant, alters the mobility of the element following its absorption by the leaf of sunflower.Because of the complex nature of the commercial products used, it was not possible to prepare a control spray treatment that contained equivalent amounts of all nutrient elements present in Kick-Off or CleanStart.At the rate used here, GroZyme contains negligible concentrations of all essential plant elements.To avoid the possibility that the effect of the foliar spray was a consequence of alleviation of secondary nutrient deficiency, all plants were grown with continuous and abundant soil nutrient.Leaf analysis was conducted and all nutrients were found to be present at adequate levels and plants showed no sign of nutrient deficiency.