1. Bio-Nano-Machines for Space ApplicationsPresented by: Ajay Ummat (Graduate Student, Northeastern University, Boston) PI: Constantinos Mavroidis, Ph.D., Associate ProfessorComputational Bio Nanorobotics Laboratory (CBNL) Dept. of Mechanical & Industrial Engineering, Northeastern University, Boston, Massachusetts
2. Researchers
Dr. M. YarmushProfessor, Biomedical Engineering, Rutgers University and MGH AtulDubeyPhD Student Rutgers UniversityGauravSharmaPhD Student Northeastern UniversityAjay UmmatPhD StudentNortheastern UniversityDr. C. MavroidisAssociate Professor Mechanical Engineering, Northeastern UniversityKaushalRegeResearch Fellow MGH / ShrinersMonica CasaliResearch Fellow MGH / ShrinersZakMegeedResearch AssociateMGH / ShrinersComputationalExperimental
3. ConsultantsDr. John Kundert-Gibbs, Clemson UniversityDr. Albert Sacco, NUDr. Ahmed Busnaina, NUBiology and Biomedical EngineeringDr. Marianna Bei, MGHDr. Jeff Ruberti, NUDr. David Budil, NUComputationalDr. SilvinaTomassone, RutgersDr. Elias Gyftopoulos, MITDr. FotisPapadimitrakopoulos, UCONNChemistry and Chemical EngineeringDr. DemetriPapageorgiou, NUMicro / Nano Manufacturing
4. Introduction and Objectives
•Identify and study computationally and experimentally protein and DNA configurations that can be used as bio-nano-machine components
•Design two macro-scale devices with important space application that will be using bio-nano- component assemblies:
–The Networked TerraXplorer(NTXp)
–All Terrain Astronaut Bio-Nano Gears(ATB)
5. The RoadmapBio SensorsDNA JointsHA a-helixA bio nano robotRepresentative Assembly of bio componentsAssembled bio nanorobotsBio nano componentsA bio nano computational cellBio nano swarmsDistributive intelligence programming & controlA Bio nano information processing componentConceptual automatic information floorAutomatic fabrication and information processingSTEP 1STEP 2STEP 3STEP 4Research Progression
6. Space Applications
Our current research is focused on two main space based applications: •Networked TerraXplorers(NTXp) –Mapping and sensing of vast planetary terrains•All Terrain Astronaut Bionano Gears(ATB) –Space radiation detection & protection system
8. Space Atmospheric Environment
•Targeting Martian environment
•AtmosphereÆCarbon-di-oxide for energy production for bionano robots.
Certain micro organisms –“Methanogens” (H + CO2)
•TemperatureÆ-140 to 20 degree C (require thermal insulation and thermally stable bio-components)
•PressureÆ6.8 millibarsas high as 9.0 millibars(1000 millibarson earth)
–Materials of sustaining internal pressures
–Bio-components which can sustain in lower pressures
–Transport mechanism through skin layer (NTXp)
9. Space Conditions
•TopographyÆScale of the bio nano machines (within meters or miles) and the area of landing and deployment
•Local dust stormsÆThe design for NTXp –capable of flowing through the local storms or resist it or both
•RadiationÆUV radiations between the wavelengths of 190 and 300 nm.
Strong oxidants on the upper surface of Mars (radiation resistant and oxidant resistant skins!)
10. Identification of Bionano Components
•Focusing on components from micro-organisms
•A positive correlation -
The degree of stability of the organism ÆThe degree of stability of their proteins
•Studying enzymes (for their dynamics and model and ease of accessibility)
-One key component is -RNA Polymerase
-Found in many micro organisms -Thermoplasmaacidophilum, Sulfolobusacidocaldarius, Thermoproteustenax, Desulfurococcusmucosus
11. Extreme Micro -OrganismsHalobacteriumD. radiodurans
•Deinococcus radiodurans
•Cold-acclimation protein –a protein from
Pseudomonas
•Some key attributes required for the
bio nano machines and components:
–Radiation resistant
–Thermal resistance (high / low)
–Acidic environment resistant
–Dry condition resistant
13. Characterization of Bionano Components
•Acontrol mechanism(chemical pathway) and its dependency on external parameters (such as, pH, temperature, chemical signals, enzymes) •The change in the external environment triggerschanges in the bionano component: -conformation changes-variations in the pattern of their self-assembly•These changes (for instance) demonstrate motionand a desired trajectory•Reversibility•Synchronizationof individual bio-components•Stochastic, less understood dynamics, complex chemical pathways
14. Computational Framework
•Identificationof the protein from the mentioned organisms Æ characterization with respect to the following three main parameters: -high temperature variations -dry conditions-space radiations•Stability analysisÆStability in various conditions is desired, such as, dry conditions, high temperature variations and radiations. •Theoverall stabilityis a complex variable of all the individual stabilitiesdry11temp22radiations33(;;....;) (;;....;) (;;....;) abjivuSfxytSgxytShxyt= = = net(;;;)drytempradiationsSFSSStβνλ∝
17. Space Radiations on Bionano System
•Radiations can produce many effects –break bonds, change the structure, destroy the amino acid residues, form other bonds•Coupling of radiationat atomic level–Hamiltonian for Radiation is coupled to the atomic system–the term coupling the electrons of the atom with the radiation. Radiations can produce many effects –break bonds, change the structure, destroy the amino acid residues, form other bonds•is the sum of A coupling terms HnÆ '' RADATOMHHHH≡++ ''H'' AnHH=Σ
19. Networked TerraXplorers(NTXp)
Mapping of vast planetary terrainsA realistic scenario where the Networked TerraXplorers (NTXp) are employed. These meshes would be launched through the parachute and these would be spread open on the target surface. These NTXps could be launched in large quantities (hundreds) and hence the target terrain could be thoroughly mapped and sensed. A single NTXp could run into miles and when integrated with other NTXPscould cover a vast terrain.
22. •External sensingÆCreation of ‘tough’ external micro channels•Reaction initiationÆPresence of charges (+/-) on the NTXp surface•SkinÆExistence of an external insulating and radiation resistive layers•Intermediary exchange layerÆSmall tubular structure for enabling active transport of ions or charges across-Connecting the micro channels and the bio-nano sensory module. •Inner sensing layerÆSensing the absorbed constituents and transferring the information of the measured parameters to the signaling module. Design Parameters & Constraints
23. •Capable of converting the sensed parameter to a parameter which could be used for signaling•FormÆflow of electrons, or variations in the concentration of ions and their gradientsSensor –Signal Dynamics
24. Flow of Signaling Parameters
{,...}iinSfg→ 1{} nioutinSpS=Σ1{(,)} noutiiSpafbg=Σ1{(,)} niiIpafbgΣ•This correspondence table decodes the input variables, f and g (or more) into pure signaling variables, say, (x, y, z). •Decoding Æreaction between the sensoryinput and the signaling module
27. The All Terrain Bionano(ATB) Gears for AstronautsOuter Layer Interacting with the Space SuitMiddle LayerSignaling & Information StorageInner Layer Interacting with the AstronautThe layered concept of the ATB gears. Shown are three layers forthe ATB gears. The inner layer would be in contact with the human body and the outer layer would be responsible of sensing the outer environment. The middle layer would be responsible for communicating, signaling and drug delivery.
28. Space Radiation –Molecular Damage
•Space radiation –damage to DNA, breaking of bonds, mutations leading to cancerous conditions
•Monitoring of the space radiations for the astronauts is the keyrequirements. Our existing design deals with radiation detection
29. Equivalence of Damage Effects
•Health hazards from the space radiations -creating equivalence energetically
31. Overall Structure of Layer Aon the ATB•Structure of the Layer A –vertical as well as horizontal directions•Non –continuumdesign (in patches) •Complimentary acceptor layer for electronic connections
32. Design of Layer -A•A surface view of the radiation detection layer– the probabilistic reaction layer is represented by spheres. •The molecular componentsutilized to make these reaction pathways •Survivalof the molecular component
33. The Number Game –Homological Settings•Represents maximum probabilityregime for the reaction. •Contains all the machinery (bionano robots) which will react with the radiation
34. Probabilistic Reaction Centers•Sphere Æmodular design strategy•Probabilistic arrangement of radiation reactants and their signaling pathways•Electron / ionic transport reactionsFe+++ + e-« Fe++
35. Electron Transfer Reactions
•Electron transfer reactions plays a key role in bioenergetics
•Fermi’s Golden Ruledescribes the rates of the reactions
•Light (radiation?) triggeredelectron transfer initiation Ætakes place in the reactioncenters of the Layer AStructure Of The Photosynthetic Reaction Centre From RhodobacterSphaeroidesCarotenoidlessStrain R-26.1
36. Radiation Resistant BacteriaThe many characteristics of D. radiodurans: •An extreme resistance to genotoxic chemicals •Resistance to oxidative damage •Resistance to high levels of ionizing and ultraviolet radiation•Resistance to dehydration •A cell wall forming three or more layersRepairs chromosome fragments, within 12-24 hoursUses a two-system processi. Single-strand annealing Æsingle strand re-connectionsii. Homologous recombination Ædouble-strand patch up•RecAprotein Æresponsible for patch up and associated reactions for DNA repair•This bacterium might contain space resistant proteins and other mechanismsDeinococcus radiodurans
37. Experimental Work
•Peptide Selection –Loop 36 (chain of 36 amino acids)
•Protein Expression
•Protein Purification
•Site-Directed Mutagenesis
•Characterizationof Protein Conformation as a Function of pH
-Circular DichroismSpectroscopy
-Nuclear Magnetic Resonance (still to perform)
38. Future Activities
•ATB gears for astronauts
a) Design the reaction mechanism for radiation detection for ATB
b) Design a detector layer complimentary to the Layer A
c) Integration with the electronic systems
•NTXp
a) Surface chemistry (water / mineral) detection network
b) Multi channel pumping / actuating mechanism for transport
c) Space condition tolerant outer skin for NTXp
39. Future Activities
•Computational framework
a) Integrate homology modeling of protein to expedite the designprocess
b) Computationally analyze the effect of radiation
c) Analyzing the radiation effects in ATB and how the ion / electron
transfereffects could be related to intensity of radiation damage.
•Experimental
a) Characterization of various bio-nano components
b) Techniques from NMR would be used to exactly characterize the
peptide structure when it changes its conformation
c) Explore the radiation resistant bacterium Deinococcusradiodurans for
possible radiation resistant bio-mechanisms and proteins
d) Experiments with carbon nano tube structures and bio-nano components
40. Publications / Presentations
•Chapter in CRC Handbook on Biomimetics-Biologically Inspired
Technologies, Editor: YosephBar-Cohen, JPL
•Chapter in The Biomedical EngineeringHandbook, 3rd Edition, Editor: M.
L. Yarmush,
•Paper Presented at the 7th NASA/DoDConference on Evolvable Hardware
(EH-2005), Washington DC, June 29 -July 1, 2005
•Interview at The ScientistVolume 18 | Issue 18 | 26 | Sep. 27, 2004
“Alternative Energy for Biomotors”
•Interview at the http://science.nasa.gov/
•Our research webpage: http://www.bionano.neu.edu
