EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.
-
Upload
sibyl-pope -
Category
Documents
-
view
217 -
download
0
Transcript of EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.
![Page 1: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/1.jpg)
EXPLORING EXPLORING BIOCHEMICAL BIOCHEMICAL ADAPTATION: ADAPTATION: Synthetic IntuitionSynthetic Intuition on a Family Farm on a Family Farm
www.carleton.ca/~kbstoreywww.carleton.ca/~kbstorey
![Page 2: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/2.jpg)
Biochemical AdaptationBiochemical Adaptation- How Animals Work- How Animals Work
• Search to identify principles of biochemical regulation across the animal kingdom
• Biochemical unity• Chemistry bkgd., NO Biology (ever) • Elastic limits of biochemistry
There are so many songs There are so many songs and only the three cords. and only the three cords.
- John Hiatt - John Hiatt
![Page 3: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/3.jpg)
A Life of Science A Life of Science Adventure Adventure
Mentors Mentors
Knut Schmidt-Neilsen, Ladd Prosser, Knut Schmidt-Neilsen, Ladd Prosser, Kjell Johansen, Kjell Johansen, Ken DaveyKen Davey, Hans Krebs,, Hans Krebs,
Gene Huber, Les Copley, Gene Huber, Les Copley, Geoff EalesGeoff Eales, A. Helix, A. Helix
Peter Peter HochachkHochachk
aa
DaveDave JonesJones
![Page 4: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/4.jpg)
DO YOUR WORK, THEN STEP BACK.THE ONLY PATH TO SERENITY.
- “Tao Te Ching” by Lao Tzu
![Page 5: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/5.jpg)
Storey Family FarmStorey Family Farm
![Page 6: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/6.jpg)
SYNTHETIC INTUITIONSYNTHETIC INTUITION1) A new mix of ideas leads to a new field:
Chemistry
Mol. Biol.
Biochem.
NMR, MRI, DSC, AFM, DSF, UV difference, Protein purification, etc.
2) Models: Zoology, Ecology, Field Trips
3) Any new set of data reorganizes itselfthrough UNRELATED pieces of the puzzleand returns as UNIQUE.
4) Salvage Solutions from Chaos:
ex. Thesis Ideas, *DATA KNOTS*
5) Time Vampire: “Students Match Projects”
Comparative Experiments
Diverse Techniques
![Page 7: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/7.jpg)
SYNTHETIC INTUITIONSYNTHETIC INTUITIONSomething Old,Something New,Something Borrowed, Some Glue
![Page 8: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/8.jpg)
SYNTHETIC INTUITION INPUTINPUT
~ Ecology
~ Natural History
~ PHYSIOLOGY
~Chemistry Analytical
~ Biochem methods
~ Mol Biol methods
~ Genes – BioInform.
- NOT Metabolism
~ Equipment Expos
~ Catalogues
~ Tools:
- PHONE (1980)
- EMAIL (1990)
~ Jan Writing
~ Touring ( R&R)
OUTPUT OUTPUT
~ Metabolic Arrangement
~ Reorganization of Metabolism
~ Adaptive Change at Pathway Level
~ Integration: multi-levels of biol. organization
~ Model Organisms as raw material
~ Intracellular: from membrane to Nucleus
BIOCHEMICAL UNITY BIOCHEMICAL UNITY
FILTERFILTER
~ Transducer
~ Organizer
~ *Revamp*
~ IDEA LENS
~ Non-sci. Stability
~ Never “Circle the Wagons”
~ COST / BENEFIT
![Page 9: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/9.jpg)
Why Am *I* Here “ “ My lab is full”My lab is full” >> Said to KBS when turned
down by PWH for a spot in his lab.
…15 minutes ( discussion) later …
“ “ Take that desk” Take that desk” >> Said to KBS when Peter
discovered that Ken had a scholarship that paid both salary and research expenses.
![Page 10: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/10.jpg)
And, StudentsAnd, Students50 MSc, 36 PhD, 11 PDFs50 MSc, 36 PhD, 11 PDFs
MSc MSc K Male, D Miller, S Korycan, R Cole, A Chakrabarti, J Duncan, R WhitwamD Kelly, D Schafhauser, C Holden, E Russell, D Douglas, A Muise, T Pannunzio,P Schade, S Greenway, M de la Roche, T English, D Lobsinger, L Jurgensen, S Lautru T Pfister, S Saeedi, M Castellarin, E Sepehr, K Yan, J Ni, L Zhenhong, A Woods, S McFadyen, J Du, J Zhang, J Zhou, L Xie, M Bouffard, J Niles, L-H Yao, J Lama, R Bell, M Mathialagan, O Aguilar, N Dawson, C Brooks, R Roufayel, S Tessier, A Letourneau, M Allan, A Holden, K Sullivan, A Mahmud, J Wu
PDFPDFJ BallantyneS RahmanB MichaelidisR FergusonSPJ BrooksM Hermes-LimaC FrankQ CaiI MoineauM BatrukovaE Kotani
PhD PhD W PlaxtonT Churchill D Joanisse Y Su J Grundy H Mehrani C Holden W WillmoreB Thatcher K Cowan J MacDonald T Bilgen S-B Wu T EnglishA FahlmanD McNallyK Larade S Eddy
D Hittel D McMullen A de Croos P Morin K AbnousM HapsatouC RamnananC Dieni A MalikA KrivoruchkoB Lant K BiggarJ Zhang C-W WuN DawsonR Bell A LetourneauS Tessier
+ 105+ 105UndergradUndergrad
ss
![Page 11: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/11.jpg)
WHY I PERSISTED WHY I PERSISTED • Synthetic Intuition Synthetic Intuition • JANET JANET • Talented Team (PhD, MSc, UG) Talented Team (PhD, MSc, UG) • Strategy (Student Wrangling) Strategy (Student Wrangling) • PDF ( Few but Key) + PDF ( Few but Key) + Luck Luck • Constant NSERC fundingConstant NSERC funding• Occasional Equipment grants Occasional Equipment grants • Big Scores (timely) CFI-OIT, NIH Big Scores (timely) CFI-OIT, NIH • Cardboard Enemies / Cardboard Enemies /
Big Talent Support Big Talent Support
![Page 12: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/12.jpg)
My Presentation : My Presentation : R&R ? Or Comedy ? R&R ? Or Comedy ?
• At Rock Shows, you want the group At Rock Shows, you want the group to play the to play the OLDOLD songs just like on songs just like on the album the album
• At Comedy Shows, if you hear an At Comedy Shows, if you hear an OLDOLD joke, you boo. You want the joke, you boo. You want the NEWNEW, fresh material. , fresh material.
Answer: Science talks are about Answer: Science talks are about tomorrowtomorrow
![Page 13: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/13.jpg)
Greatest Hits: (Vol 1)Greatest Hits: (Vol 1)“High Tides & Green Grass” “High Tides & Green Grass”
The early days The early days • Comparative regulation of glycolysisComparative regulation of glycolysis• Methods in Enzymology (purification) Methods in Enzymology (purification) • Exercise muscle metabolism: insects & cephalopods Exercise muscle metabolism: insects & cephalopods • Octopine (Octopine (Storey cycleStorey cycle), alanopine & strombine ), alanopine & strombine • Glycolytic Enzyme ComplexGlycolytic Enzyme Complex• Bound water in metabolism Bound water in metabolism • Reversible phosphorylation control of Reversible phosphorylation control of
metabolic enzymes ( Novel) metabolic enzymes ( Novel) • Phosphagen effects on enzymes Phosphagen effects on enzymes
• PFK polymers & F2,6PPFK polymers & F2,6P22
![Page 14: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/14.jpg)
Greatest Hits: (Vol 2) Greatest Hits: (Vol 2) Anoxia ToleranceAnoxia Tolerance
• Anti-Pasteur Effect (Anti-Temperature !) Anti-Pasteur Effect (Anti-Temperature !) • Coordinated Metabolic Rate Depression (MRD)Coordinated Metabolic Rate Depression (MRD)• Anabolism Anabolism followsfollows Catabolism in MRD Catabolism in MRD • Reversible phosphorylation of glycolytic Reversible phosphorylation of glycolytic
enzymes: Gly phos, PFK, PK, etc. enzymes: Gly phos, PFK, PK, etc.• Protein kinases: PKA, PKG, MAPKs, AMPK, etc.Protein kinases: PKA, PKG, MAPKs, AMPK, etc.• Anoxia-induced gene expressionAnoxia-induced gene expression• Antioxidants – adaptation to variable oxygenAntioxidants – adaptation to variable oxygen
![Page 15: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/15.jpg)
Greatest Hits: (Vol. 3) Greatest Hits: (Vol. 3) Cold & Freezing SurvivalCold & Freezing Survival
• Deep supercooling by cold-hardy insects Deep supercooling by cold-hardy insects • Freeze tolerance:Freeze tolerance:
- insects & molluscs - insects & molluscs
- frogs, turtles, lizards, snakes- frogs, turtles, lizards, snakes• Biochemistry of cryoprotectants Biochemistry of cryoprotectants • Adaptive evolution from underlyingAdaptive evolution from underlying
anoxia & dehydration tolerances anoxia & dehydration tolerances• Freeze responsive gene expressionFreeze responsive gene expression• Novel proteinsNovel proteins
![Page 16: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/16.jpg)
Unique Animal Stress ModelUnique Animal Stress ModelVertebrate whole-
body freeze tolerance
Tissue cryopreservation
Tolerance of extreme ischemia and
hyperglycemia
![Page 17: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/17.jpg)
Greatest Hits: (Vol. 4) Greatest Hits: (Vol. 4) HibernationHibernation
• Regulated MRD drives body temperature downRegulated MRD drives body temperature down• Reversible enzyme control in torpor-arousal cyclesReversible enzyme control in torpor-arousal cycles• Cold adaptation of mammalian enzymesCold adaptation of mammalian enzymes• Polysome dissociation, mRNA storagePolysome dissociation, mRNA storage• Micro RNA Micro RNA • Gene screening, epigenetic controlsGene screening, epigenetic controls• Antioxidant defense (Tf) Antioxidant defense (Tf) • Atrophy resistance Atrophy resistance
![Page 18: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/18.jpg)
Greatest Hits: (Vol. 5) Greatest Hits: (Vol. 5) EstivationEstivation
• MRD parallelsMRD parallels estivation = low oxygen / anoxia estivation = low oxygen / anoxia
• Phosphorylation also controlsPhosphorylation also controls - ion motive ATPases (NaK, Ca) - ion motive ATPases (NaK, Ca) - novel enzymes - novel enzymes - protein synthesis flux generators - protein synthesis flux generators - transcription factors - transcription factors
• Involvement of protein kinases – Akt,Involvement of protein kinases – Akt, AMPK, MAPKs, PKA/PKG AMPK, MAPKs, PKA/PKG
• Role of FOXO transcription factorsRole of FOXO transcription factors• Urea effects on enzymesUrea effects on enzymes
![Page 19: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/19.jpg)
www.carleton.ca/kbstoreywww.carleton.ca/kbstorey
• Animal stories• Publications• Research Interests• Students & projects• Media•Textbook with former students
Greatest Greatest
Hits: Hits: Full Full CollectionCollection
![Page 20: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/20.jpg)
Best Experiment EVER ! Best Experiment EVER !
CSZ U. Ottawa
1983
J.E.StoreyCarleton U.
![Page 21: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/21.jpg)
Estivation
METABOLIC RATE METABOLIC RATE DEPRESSIONDEPRESSION
Diapause
Freezing
Anoxia
Hibernation
![Page 22: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/22.jpg)
Crayfish
![Page 23: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/23.jpg)
Principles of Principles of Metabolic Rate DepressionMetabolic Rate Depression
• Transcriptional + translational + PTM Transcriptional + translational + PTM • Anabolism Anabolism followsfollows Catabolism in MR Catabolism in MR • Coordinated suppression: gene expression, Coordinated suppression: gene expression,
protein synthesis, biosynthesis, cell cycle, etc. protein synthesis, biosynthesis, cell cycle, etc.• Reversible phosphorylation of key enyzmes,Reversible phosphorylation of key enyzmes,
ion channels, transcription factors, etc. ion channels, transcription factors, etc.• Stress-activated protein kinases Stress-activated protein kinases
Cell preservation in hypometabolismCell preservation in hypometabolism• Antioxidant defenses, iron sequesteredAntioxidant defenses, iron sequestered• Chaperone proteins Chaperone proteins
![Page 24: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/24.jpg)
GENESGENES
Transcription
RNAsRNAs
Control byControl bytranscriptional regulationtranscriptional regulation
Control byControl bytranslational regulationtranslational regulationTranslation
PROTEINSPROTEINS(ENZYMES)(ENZYMES)
Control byControl byproteasesproteases INACTIVEINACTIVE
ENZYMEENZYME
NoModification
FUNCTIONALFUNCTIONALENZYMESENZYMES
Covalentmodification
Degradation
Control by post-Control by post-translationaltranslationalmodificationmodification
ACTIVEACTIVEENZYMESENZYMES
Inhibitionand
Activation
Control at level ofControl at level ofenzyme functionenzyme function
www.carleton.ca/~kbstoreywww.carleton.ca/~kbstorey
![Page 25: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/25.jpg)
GENE CHIPS TRANSCRIPTION FACTORPROFILING
Data LeadsData Leads
ELISAs in plates
Confirm by EMSA
Confirm byRT-PCR,
Northern blots
TfDownstream genes
ROLE & CONTROL OF SYSTEM
Transgenics
Cell AssayRNAi Knock out Epigenetics
FUNCTIONAL ASSAYS
Protein levels - enzyme assay - antibodies : protein - functional analysis e.g. HIF EPO
![Page 26: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/26.jpg)
Where do we go from Where do we go from here? here?
• Human applications of MRD research • Novel phosphorylations• Atrophy, hypertrophy -- autophagy for survival • Turning it all off -- microRNA• Epigenetics & adaptation • Life span extension• Antioxidant defense• Cell cycle suppression• Unity through evolution
NOW: finally !!! NEW NOW: finally !!! NEW DIRECTIONS DIRECTIONS
![Page 27: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/27.jpg)
Hibernation and medicineHibernation and medicine
Primates !!
![Page 28: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/28.jpg)
Novel phosphorylations Novel phosphorylations
PPPP PP
PP
PiPiProtein
Phosphatase
ATPATP ADPADPProtein Kinase
![Page 29: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/29.jpg)
Atrophy – HypertrophyAtrophy – Hypertrophy
![Page 30: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/30.jpg)
Turning it all Turning it all offoff
![Page 31: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/31.jpg)
Epigenetics in AdaptationEpigenetics in Adaptation
![Page 32: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/32.jpg)
Life span Life span extensionextension
![Page 33: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/33.jpg)
Ukrainian connectionUkrainian connection- Metal & herbicideMetal & herbicide
effects on fisheffects on fish- Antioxidant defense- Antioxidant defense
![Page 34: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/34.jpg)
Unavoidable metabolic costs Unavoidable metabolic costs
![Page 35: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/35.jpg)
Unity through Evolution Unity through Evolution
WWCeDWWCeD
![Page 36: EXPLORING BIOCHEMICAL ADAPTATION: Synthetic Intuition on a Family Farm kbstorey.](https://reader035.fdocuments.net/reader035/viewer/2022062804/56649ee75503460f94bf8a94/html5/thumbnails/36.jpg)
ONWARDS !ONWARDS !
pH low high
MW
low
hig
h