"What I can't make I don't comprehend": The parallel synergistic pathways of outline and revelation.

Uploaded on:
Category: Home / Real Estate
"What I can't make I don't comprehend": The parallel synergistic pathways of configuration and revelation.
Slide 1

“What I can\'t make I don\'t understand”: The parallel synergistic pathways of configuration and revelation Michael L. Simpson Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, TN 37831 Materials Science and Engineering Department, The University of Tennessee, Knoxville, TN 37996 NSF Workshop on Molecular Communication: Biological Communications Technology February 20-21, 2008

Slide 2

Grand Challenges DOE – BES as of late discharged rundown of ‘grand challenges”

Slide 3

Biological frameworks 4B years of brutal companion audit Scale (thickness), Complexity (network) Components Complexity in capacity for the most part involves multifaceted nature in the wiring….

Slide 4

Understand Design Questions for S2 How do organic elements impart? How is natural data encoded onto and decoded from atoms? What are the repeating architectures of organic correspondences? What are the heartiness delicacy exchange offs in natural correspondences frameworks? In what manner can diverse organic frameworks be interfaced to upgrade correspondence? How might correspondence components utilized by organic elements be connected to make a manufactured correspondence framework utilizing natural materials?

Slide 5

Understand Design This discussion What is the framework environment? Past 1 st close estimations Information scene (commotion is all around) Communicating in a group Architectures that have advanced in this environment Bow ties, power, and delicacy Poster tyke for organic correspondences, majority detecting With inadequate learning, how would we outline in this environment? Top-down Bottom-up

Slide 6

Transmitter Receiver Channel gene1 gene2 From a frameworks view correspondence has three fundamental players First request rough guesses – framework wide high devotion Transmitter encodes with high loyalty (collector translates) data in size or condition of an atomic populace/fixation There is no ‘uncertainty’ in the data Free dispersion of data through a quiet channel Activity of gene2 straightforwardly relative to movement of gene1 (e.g. Slope expression)

Slide 7

Tat A Rev t 1/2 = 40 hrs Tat Vpu Nef 5’LTR Gag Pol Env 3’LTR Vif Vpr Information Processing by Cells: Beyond First Approximations Transient driven capacity “rates” and “concentrations”. responses dispersion limitedin an all around blended cell. Our point: To measure cell data preparing at the level of individual occasions in space and time. Quality action (RNA/Protein) 40 hrs Lysis ON +FB Latency Time Ido Golding, Dept. of Physics, UIUC Leor Weinberger, UCSD

Slide 8

Gene P mRNA rot commotion k R Transcription clamor * mRNA k P Translation clamor Protein rot clamor * Protein Noise is all over the place Poisson forms σ 2 = <M> Gene expression is bursty σ 2 ~ b<M> Transcriptional control is much noisier than Hill energy demonstrates Extrinsic commotion Correlated commotion that couples into all quality circuits Is commotion dependably ‘bad’? May pass on the genuine instability in data Exists in the setting of an exceptionally organized complex framework what are the ‘systems’ properties of commotion?

Slide 9

broad take a gander at clamor Noise in yeast proteins Noise structure is more mind boggling Noise is 2-d: (size of changes); and connection (length of time of variances) High populace & high commotion? Why? Simpson, et al., Proc. Nat. Acad. Sci. 100 , 4551-4556 (2003). Austin, et al. Nature , 439 , 608-611 (2006). Bar-Even, et al., Nat Genet , 38 , 636-643 (2006). Newman, et al. Nature , 441 , 840-846 (2006).

Slide 10

C onservation and conveyance of stochasticity Fundamental inquiry: How ought to stochasticity be dispersed and directed Uniformly appropriated? Dispersed by capacity sort? Is stochasticity constantly minimized? However, Is limited ~50M atoms, couple of thousand distinct proteins Total stochasticity is saved, yet it can be unequally dispersed over the segments

Slide 11

Sender Receiver Channel gene1 gene2 gene1 gene2 gene3 The data scene is swarmed and noisy…..so is the physical scene Marsh,et al. PNAS, 98, 2399-2406 , 2001

Slide 12

Bow ties, strength, and delicacy Csete and Doyle, Trends in Biotechnology , 2004

Slide 13

The p53 Network – Bow-Tie Signaling Architecture Eric Bachelor, Harvard DNA harm repair Apoptosis Cell cycle capture Senescence g radiation Stalled replication forks UV radiation Ribosomal Stress Oncogenes p53

Slide 14

Varied p53 Dynamic Responses to DNA Damage g radiation UV radiation DNA Double Strand Breaks Single Strand DNA ATM ATR Chk1 Chk2 Series of Undamped p53 Pulses Graded p53 Pulses p53 Mdm2 Wip1

Slide 15

LuxR O N H O Pheromone-interceded control of bioluminescence in Vibrio fischeri is a basic “quorum sensing” administrative circuit… “lux box” luxR luxI luxC luxD luxA luxB luxE luxG FMNH 2 + O 2 + RCHO RCOOH + FMN + H 2 O + light LuxI 3-oxo-C6-HSL 3-oxo-C6-HSL Eric Stabb, University of Georgia

Slide 16

…or is it? 3OC6 C8 AI-2 AI-2 AI-2 AI-2 AI-2 OM AI-2 LuxP C8 acnB phoQ ainS hns lon guaB pstA/pstC tfoX topA tRNA LuxQ IM AinR  54 Hfq C8-LuxR P-LuxO sRNA’s (C8 and AI-2 lead to less LuxO-P) 3OC6-LuxR LuxO LuxU litR LuxR LitR luxR luxI luxC luxD luxA luxB luxE luxG “lux box” LuxS ArcA/ArcB LuxI bioluminescence OH HO O AinS B - O N HO H O HO O N (3OC6) H O (AI-2) (C8) C8 3OC6 AI-2 Eric Stabb, University of Georgia

Slide 17

Biological frameworks Scale (thickness), Complexity (network) Top-down Understanding framework environment & rewiring multifaceted nature Components Bottom-up Construction of unpredictability The conversion of configuration and revelation: System plan philosophy? “….often more is found out about existing framework structural engineering through an endeavored update than through examination alone….”

Slide 18

Design space Design space Design space: Around the edges inflexibility pliancy versatility Kobayashi, H. et al. (2004) Programmable cells: Interfacing normal and built quality systems. Proc. Natl. Acad. Sci. U. S. A. 101, 8414–8419 Whole-Cell Synthetic Biology (Jeff Hasty in S2)

Slide 19

Replacing the center inflexibility unbending nature versatility pliancy Yin et al., Nature , Jan. 2008

Slide 20

PORE DNA Transcription SENSOR Protein Translation PORE Images from www.nsf.gov A tad bit of both: cell imitates Material Synthesis, Information Processing, Energy Conversion M. J. Doktycz, ORNL - Replace with engineered smaller scale and nano-manufactured structures - Define cell size - Predictably control material flux - Defines volume (focus) - Controls presentation and arrival of materials Membrane - Gather info - Signal intensification - Logic - Generate yield - Metabolize vitality Molecular Networks - DNA based guidelines - Modulate quality duplicate number, control codon utilization, cross reactivity… - Cell free interpretation/interpretation A conceivably widespread stage for detecting, inciting, producing vitality, figuring and interfacing to regular frameworks A beginning stage for comprehension incorporated systems,the impact of scale on system capacity, and the making of commonsense gadgets

Slide 21

Sealed Container 120 ng/µl DNA 60 ng/µl DNA Control 25 min 35 min 45 min Nano-empowered engineered science Macromolecular swarming and association 10–40%/V of cell volume is swarmed with macromolecules Reaction rates are quickened, viable fixations are changed, and movement coefficients are modified comprehend transport in swarmed situations uncover diffusional flux at the nanoscale Transport rates can rely on upon time/separation in swarmed situations Assembly and testing of hereditary systems and cell-cell correspondence DNA build containing a quality for GFP and a T7 promoter are set in the phone emulate E. coli S30 cell free concentrate and little metabolites are included Fowlkes et al., Nanotechnology 17 (22): 5659-5668 (2006)

Slide 22

Speakers for S2 Eric Stabb – Quorum detecting Eric Bachelor – P53 necktie flagging building design John Doyle – Robustness and delicacy Leor Weinberger – Decision making in individual cells/transient driven capacity Ido Golding – Information preparing in cells Jeff Hasty â€

View more...