1 DOE Bioenergy Center proposal Discussion sections November 21, 2006 George Church and John Aach Department of Genetics Harvard Medical School [email protected]

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DOE Bioenergy Center proposalDiscussion sections

November 21, 2006

George Church and John Aach

Department of Genetics

Harvard Medical School

[email protected]

CONFIDENTIAL

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Things to consider in each session

• Does this project group have a different priority than others?

• Are there synergies between these projects or with projects in other groups?

• Are there overlaps which should be resolved?

• What enabling technologies can these make use of– low cost DNA or RNA resequencing

– low cost DNA synthesis from oligos

– artificial evolution

– metagenomics

– single-cell sequencing

– membrane protein production and purification

– computational modeling

• Can specific economic benefits be assigned to any of these projects?

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Project list: Plants

2 AgrividaM. Raab (F. Ausubel)Efficient pre-harvest expression and accumulation of combinations of cell wall degrading enzymes in plants, and their post-harvest stability and effectiveness

enabling_technology

7 Brookhaven National LabC-J LiuAssess the roles of O-acylation and -deacylation enzymes in biomass formation and identify modifications that enhance lignocellulose degradation

real_step

8 Chromatin, Inc. D. PreussImprove plant biofeedstock characteristics using autonomous mini-chromosomes

enabling_technology

23 Penn State D. Braun, D. CosgroveGenetic Approaches to Improved Biomass Feedstocks [Reduced Silica, Higher Degradability

real_step

22 Penn State D. Braun, M. GuiltinanGenetic & Biochemical Analyses of Carbon Partitioning in Plants

real_step

24 Penn State D. Cosgrove, M. Buanafina, M. Tien, J. Carlson, H. Liang, K. HooverTechnologies for Generating Cellulosic Biomass for Faster Saccharification

breakthrough

25 Penn State M. Buanafina, M. Guiltinan, J. CarlsonPlant Transformation Facility enabling_technology

21 Penn State W. Curtis (P. Laible, D. Hanson)

Explore "trickle-down" bioreactor as mechanism for increasing algal biomass productivity by orders of magnitude in support of biodiesel, and for optimizing Rhodobacter-based membrane protein expression system

breakthrough

37 U. Florida, Michigan TechS. Joshi, L. IngramChanging plant cell wall composition for energy crops real_step38 U. KentuckyJ. ChappellC30-34 hydrocarbon-enhanced Plant and algae biomass breakthrough

40 U. Mass AmherstD. Schnell, (O. Parkash, T. Baskin, J. Normanly, S. Herbert, R. Prostak, Optimization of Feedstocks for Consolidated Bioprocessing to Generate Biofuels and Bioproducts

real_step

53 INL through PSUPLACEHOLDER: projects not yet defined real_step54 SC Vance RNA silencing in Arabidopsis enabling_technology30 Penn State T.L.Richard, P. Adler, G. Roth, J. Carlson, G. Caufmann, W. Curtis, A. Demirci, A. Zydney, A. Boehman, C. Song, J. Perez, J.R. Hess, C. RadtkeFields-to-Wheels Bioenergy Testbed Facility process_modeling

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Saccharification and CBP

4 Boston U. J. CollinsIdentification of efficient artificial cellulosomes using phage display

breakthrough

12 Harvard Med SchoolF. Ausubel (A. Diener, C-J Liu)Optimization of plant-pathogen derived CWDEs for biofuel feedstocks

real_step

13 Harvard Med SchoolW. ShihIdentification of efficient artificial cellulosomes using in vitro selections of very highly combinatorial libraries of DNA-display-based cellulosome mimics

breakthrough

26 Penn State P. Cirino, C.D. Maranas, S. BenkovicProtein Engineering for Biofuels: Enzyme engineering of (hemi)cellulases

real_step

32 U. FloridaL. Ingram &c.Reducing dependence on fungal cellulase (reduce cost of polymer hydrolysis): Explore use wood degrading insects

real_step

33 U. FloridaL. Ingram &c.Reducing dependence on fungal cellulase (reduce cost of polymer hydrolysis): integration & expression of glycohydrolases & uptake systems (dimers/trimers)

real_step

34 U. FloridaL. Ingram &c.Reducing dependence on fungal cellulase (reduce cost of polymer hydrolysis): B. coagulans

real_step

47 U. WisconsinT. JeffriesCharacterize and create cellulase and xylanase hypersecreting strains of fungi.

real_step

39 U. MaineH. Pendse, (S. L. Hsu, [UMass], P. Millard, A. van Heiningen, J. Genco)On-site Integration of Consolidated Bioprocessing into an Existing Industrial Facility

process_modeling

41 U. Mass AmherstJ. Blanchard, (S. Leschine, M. Henson)Optimization of C. phytofermentans for the Direct Conversion of Cellulosic Biomass to Ethanol

real_step

42 U. Mass AmherstS. Leschine, (D. Schnell, L. McLandsborough, J. Blanchard, M. Henson)A Novel Bacterial Catalyst for Consolidated Bioprocessing of Biomass to Ethanol

real_step

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BP

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Fermentation

6 Boston U. J. CollinsSystems & synthetic biology platform for reverse and forward engineering of regulatory networks for bioenergy

real_step

11 Harvard Med SchoolG. Church

Complete development of and apply High Throughput Mutation Detection - Combinatorial Variation technology to improve yield and production characteristics of a diverse set of biofuel-generating microbes

real_step

36 U. FloridaL. Ingram &c. (G. Church)Metabolic engineering for inhibitor resistance / sugar co-utilization + pretreatments

real_step

31 U. FloridaL. Ingram &c. (G. Church)Merging fermentation of hemicellulose hydrolysates (dilute acid) with cellulose hydrolysate fermentation

real_step

35 U. FloridaL. Ingram (with G. Church)Reduce water use by integrating re-utilization and production of co-products, and increasing ethanol tolerance

real_step

46 U. WisconsinT. Jeffries

Characterize and create P. stipitis with improved fermentation efficiency and production environment tolerance using combinatorial exploration of expression and effective mutation space

real_step

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Economic and process modeling; process improvement

30 Penn State T.L.Richard, P. Adler, G. Roth, J. Carlson, G. Caufmann, W. Curtis, A. Demirci, A. Zydney, A. Boehman, C. Song, J. Perez, J.R. Hess, C. RadtkeFields-to-Wheels Bioenergy Testbed Facility process_modeling

44 U. Mass AmherstM. Henson, (M. Malone, TJ Mountziaris, D. Ford)UMass Process Engineering and Design Component

process_modeling

43 U. Mass AmherstS. Auerbach, (G. Huber, Integration of Chemical Catalysis into a Biorefinery unclassified

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Alternative biofuels / paradigms

• Do we need to have a general strategy for dealing with projects which yield alternative biofuels (including non-liquid or non-transportation fuels), or different pathways (including non-biological), or different technologies? Or is it case-by-case?

19 Harvard Med SchoolP. SilverIncorporate pathways into S. cerevisiae that support bio-hydrogen generation

breakthrough

28 Penn State D. A. Bryant, J. H. GolbeckEngineering Novel Metabolic Capabilities in Cyanobacteria for Bioenergy

breakthrough

27 Penn State J.G. Ferry, P. Cirino, J.J. ReganMethane and Syngas Fermentation breakthrough

29 Penn State J.M. Regan and B.E. LoganMicrobial Fuel Cells for Coupled Energy Recovery and Water Reuse

breakthrough

48 UCLA A. DienerLipid accumulation in Fusarium breakthrough

21 Penn State W. Curtis (P. Laible, D. Hanson)

Explore "trickle-down" bioreactor as mechanism for increasing algal biomass productivity by orders of magnitude in support of biodiesel, and for optimizing Rhodobacter-based membrane protein expression system

breakthrough


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38 U. KentuckyJ. ChappellC30-34 hydrocarbon-enhanced Plant and algae biomass

breakthrough

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Pretreatment, Extraction, Use

• These areas are not well represented. Only projects are:

• Instead, many projects attempt to deal with them via upstream or downstream modifications, e.g., – Modify plants to reduce pretreatment– Modify microbes to be tolerant to inhibitors and conditions

generated by pretreatment– Reduce extraction costs by increasing EtOH tolerance

• Is this acceptable, or do we want more projects specifically addressed to them?


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56 Penn State T. RichardPLACEHOLDER: Biological pretreatment via silage real_step

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Enabling science and technology3 Argonne National LabP. Laible, D. Hanson

Improved production of membrane proteins relevant to biomass to biofuels processing

enabling_technology

5 Boston U. D. SegreBioenergy-relevant extensions of Flux Balance Analysis models and their applications to Center organisms

enabling_technology

9 HarvardC. MarxEvolving tradeoffs: role of selective regime on specialization and adaptation

enabling_technology

10 HarvardC. MarxThe origin of cooperation and coevolution: selection of increased metabolite production in spatially-structured, cross-feeding microbial consortia

enabling_technology

14 Harvard Med SchoolG. ChurchGeneration of Flux Balance Analysis models for Center organisms

real_step

15 Harvard Med SchoolG. ChurchImproved and multiplex single cell genome sequencing on environmental samples

enabling_technology

17 Harvard Med SchoolG. ChurchDevelopment of engineered RNA molecules to control gene expression, sense metabolites and optimize the properties of metabolic pathways

enabling_technology

18 Harvard Med SchoolG. ChurchGenome re-engineering (rEcoli) enabling_technology

16 Harvard Med SchoolW. ShihStructures of transporters using DNA-nanotube liquid crystals

enabling_technology

20 MIT P. Chisholm, M. Polz, E. AlmGenomic structure, metagenomics, horizontal gene transfer, and natural diversity of Prochlorococcus and Vibrio (GTL Systems Biology project)

enabling_technology

45 U. MichiganN. Lin Development of alternative modeling techniques enabling_technology

49 Harvard Med SchoolSarracino, KucherlapatiPLACEHOLDER: service cost referred to by Marx but not quantified

enabling_technology

50 MIT Endy, Knight, RettbergPLACEHOLDER: Synthetic Biology enabling_technology51 MIT JacobsonPLACEHOLDER: Genome Engineering enabling_technology52 UCSD Palsson PLACEHOLDER: Flux balance modeling enabling_technology

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Open discussion

• ???

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Budget

We intend the preliminary management team to work out the budget.

Here we want input on:• Should some project areas / pathway steps get more

/ less priority?• In what way should we accommodate companies in

the budget?• How should we manage the budget process going

forward?

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Next steps

Preliminary management team • Needs to be defined ASAP• First duties of PMT: letter of intent, review / reorganize

budget

Everyone else• Get ‘plugged in’ (email distribution list, wiki access)• Flesh out, reformat project write-ups by November 30.• Disclose contacts / collaborations with other BRC

groups / BP

Up and coming• Review of integrated proposal

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Thank you for coming &

Enjoy your Thanksgiving holiday!

George and John

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Documents

1 DOE Bioenergy Center proposal Discussion sections November 21, 2006 George Church and John Aach Department of Genetics Harvard Medical School [email protected]