DEVCOM ARL.pdf

UNCLASSIFIED//APPROVED FOR PUBLIC RELEASE

U.S. ARMY COMBAT CAPABILITIES

DEVELOPMENT COMMAND –

ARMY RESEARCH LABORATORY

Dr. Margaret Hurley

Research Chemist, Biomaterials Team Lead

ARL CCDC

14 December 2020

Biotechnology Branch and the Transformational

Synthetic Biology for Military Environments

Essential Research Program TRANSFORME

Unclassified

OVERARCHING CHALLENGES

FOR DOD SYNBIO

Synthetic biology enables game-changing advances in the lab

Must translate the same level of success to the field

Synthetic Biology Essential Research Project

Transformational SynBio for Military Environments (TRANSFORME)

How will Synthetic Biology Transform the Future Operating Environment?

Control

In the environment?

Harness low energy routes for production?

Provide rapid countermeasures?

Re-program indigenous biology?

Target and trigger effects?

Adapt at operational tempo?

THRUST 1 –SYNBIO TOOLS EXAMPLE

ARMY BIOLOGICAL FOUNDRY

Nucleic acid sequencing (GSAF)

• NGS – Illumina/Nanopore

• RNAseq

• Classical Sanger

Gene synthesis

• Chip synthesis

• Column synthesis

• Fully automated assembly

Microscopy & Imaging

• Confocal

• FACS and emulsion sorting

• EM (Cryo-, TEM, SEM)

Texas Advanced Computing Center and DOD HPC

• Stampede/Lonestar/Ranger

• Molecular simulations

• Machine learning Mass spectrometry

• Proteomics

• Metabolomics

• LC, GC, MALDI

UTEX Culture Collection

• Largest collection (>3000 strains)

• Most diverse

• Optically active

Facilities and foundry capabilities

SECURE FOUNDRY

High throughput DNA synthesis, genetic assembly, strain construction, and testing

APPLICATIONS

Rapid response biologics

Forward engineering of biological systems

(cells, organisms, microbial consortia, etc.)

Biological materials engineering

G O

A L

Develop agile, modular foundry for key military environments & specialty, allowing US to out innovate and counter adversary

THRUST 1 SYNBIO TOOLS EXAMPLE

BIOPROSPECTING AND ENGINEERING NEW

CHASSIS

Bioprospecting Activity

Screening

Characterization Engineering Functional

Bioproduct

Bioproduction Transition/

Commercialization

• Exploit massive available diversity of biological functions.

• Biological strains and components can be obtained from a variety of sources.

• Natural environment

• Culture

Collections

• Sequence databases

Screen for desired function

• Identify candidate leads for further analysis and application.

• Growth assays

• Enzyme assays.

• Natural product production.

Characterize candidate leads

• Genome

Sequences

• RNAseq

• cDNA Libraries

• Transformation assays.

• Growth assays

• ‘-Omics’

• Enzyme assays.

• Structural analysis

• Modeling

Engineer/improve candidate lead functionality

• Bio-parts toolkit design/creation

• Automated high-throughput construct assembly

• High-throughput screening

• Directed evolution

• Combinatorial library creation

• Degenerate library creation

• Rational design

Verification, characterization and application of bio-products.

• Physical characterization of bio-lead.

• Functional validation of desired function and properties.

• Refinement of functional leads to specific applications.

Scale up

• Process engineering for producing bio-product at scale.

• Pilot production and intermediate scale testing of functional materials

Mature Product

• Incorporation of bio-product into functional materials.

• Integration into

• Commercial-scale applications.

• Application to field environments.

THRUST 2

SCALEABLE HIERARCHICAL CONTROL

Initial applications toward EM/EO skins

Leverage SynBio to make materials with controlled structures across all lengths

3D Network assemblyPeptide-driven nanoscale control

Luo et al. Energy & Environ. Sci., 2017

Adams et al. Adv. Mat. 2013

Sequence-specific molecular tuning

Integrate with traditional material science to allow rapid manufacturing and transition to Army platforms Longer term biology will enable far-forward device assembly to meet future Army operating concepts

Xiao et al. ACS Nano 2015, 9, 5454

Knorr et al. Langmuir 2016, 32, 4370−4381

Nagar et al. Optica 5, 2 2018

THRUST 2

SPANNING MATERIALS SPACE

Quasi-static, impact, ballistic

Inorganic structures

Magnetosomes

Organic structures

Cellulose and Silk

Organic Compounds

Melanin Hybrid Systems

Dong et al Biofunctionalized Cecllulose Nanofibrils ACS App Bio Mat http://dx.doi.org/10.1021/acsabm.9b00295

Furubayashi et al

THRUST 2

SPANNING MATERIALS PERFORMANCE

SPACE

Environmental

Extremes

Mechanical

Extremes

Quasi-static, impact, ballistic

High pressure

Launch conditions

Temperature

Humidity

Life Time

Electrical/Optical

Chem/Bio/Radiological

Composites

Additive Materials

Adhesives, Epoxies

Metals, Semiconductors

Ceramics-Coatings, Glass, Cement

Avionics

Soft Materials-

Polymers

Cost of corrosion related system failures ~ 1/5 of the DoD maintenance budget ($20B/year) and causes down-time of critical assets.

Without Acceleration

THRUST 3 CONTROL IN MILITARY

ENVIRONMENTS

What assets can be degraded within: Minutes?

Hours? Days? Weeks? Months?

What approaches can be used to counter corrosion?

XPORT ENTRAP: XPORT mediated

ENhanced TRAnsfer Platform

Droplet Enhanced Microbial DNA Transfer

SAMPLE WORK AND COLLABORATIONS

Discovery of Targeted Material Binding Microorganisms

Using a Centrifugal Microfluidic Platform

Han et al submitted to Advanced Materials

Brophy et al “Engineered integrative and conjugative elements for efficient and inducible DNA transfer to undomesticated bacteria” Nature microbiology, 1, 2018

Meyer et al “Organism Engineering for the

Bioproduction of the Triaminotrinitrobenzene (TATB)

Precursor Phloroglucinol (PG). “ ACS Synth Biol 8 (12), 2746-2755. Agnew et al “Protein-Catalyzed Capture Agents” Chem. Rev., 2019

Protein Catalyzed Capture Agents

SAMPLE WORK AND COLLABORATIONS

Furubayashi et al "Genetic Tuning of Iron Oxide

Nanoparticle Size, Shape, and Surface Properties in

Magnetospirillum magneticum," Advanced Functional

Materials (2020)

Hong et al “Biofunctionalized Cellulose Nanofibrils Capable of Capture and

Antiadhesion of Fimbriated Escherichia coli”

ACS Appl. Bio Mater. 2019, 2, 7, 2937–2945 https://doi.org/10.1021/acsabm.9b00295

SAMPLE WORK AND COLLABORATIONS

Perisin and Sund “Human gut microbe co-cultures have greater potential than monocultures for food waste remediation to commodity chemicals” Scientific Reports volume 8, Article number:

15594 (2018)

Schwalm et al Developing a Microbial Consortium for Enhanced

Metabolite Production from Simulated Food Waste Fermentation

2019, 5(4), 98; https://doi.org/10.3390/fermentation5040098

Warner, C.M., et al 2020. Synthetic Biology:

Research Needs for Assessing Environmental

Impacts. In “Synthetic Biology 2020: Frontiers in Risk

Analysis and Governance”. Springer, Cham. pp. 19-

50.

QUESTIONS?

Contacts

Dr. Margaret Hurley General margaret.m.hurley12.civ@mail.mil

Dr. Randi Pullen Thrust 1 randi.m.pullen.civ@mail.mil

Dr. Joshua Orlicki Thrust 2 joshua.a.orlicki.civ@mail.mil

Dr. Meagan Small Thrust 3 meagan.c.small.civ@mail.mil