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Fated ? Paradoxes August 4, 2013 Dr. Katie Galloway Do your genes decide your fate?

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Presentation on theme: "Fated ? Paradoxes August 4, 2013 Dr. Katie Galloway Do your genes decide your fate?"— Presentation transcript:

1 Fated ? Paradoxes August 4, 2013 Dr. Katie Galloway Do your genes decide your fate?

2 Fat gene?

3 Infidelity gene?

4

5 Identifies-meaningless-correlations gene?

6 A bottom-up approach ““We are survival machines – robot vehicles blindly programmed to preserve the selfish molecules known as genes.” – Richard Dawkins, biologist

7 MoleculesNetworksCellsTissuesSystemsOrganism A Reductionist view of Biology Environment & society Input: Initial conditions Output: Fate

8 MoleculesNetworksCellsTissuesSystemsOrganism Environment & society Input: Initial conditions Output: Fate Layers of design

9 Gene expression: Running genetic program DNA mRNA protein Promoter: Controls production RNA from DNA pX

10 Epigenetics and structure of DNA pter-4-dna-chromosomes-and- genomes/deck/

11 Loose packing of DNA turns on genes

12 pter-4-dna-chromosomes-and- genomes/deck/ Tight packing of DNA turns off genes 10,000 fold packing during cell division!

13 3D structure of the genome influences how sets of genes interact pter-4-dna-chromosomes-and- genomes/deck/

14 DNA wrapped for tangle free, dynamic loosing and rewrapping

15 Gene expression: Running the program DNA mRNA protein pX Promoter: Controls transcription of DNA to RNA Non-coding RNA: Controls processing of mRNA into proteins

16 Percent of non-coding DNA increases with organism complexity Mattick, J.S. Scientific American 2004

17 “Junk DNA” is not so “junky” Mattick, J.S. Scientific American % of human non-coding DNA is translated into RNA

18 DNA mRNA protein ~20,000 genes ~1,000,000 proteins Diversity of proteins 50x > genes!

19 DNA translation Brain protein Liver protein RNA Not the size of your genome, but how you use it

20 Natural RNA control systems intervene in gene expression to direct cellular fate DNA transcription pre-mRNA editing, splicing mRNA translation Brain protein Liver protein silencing Post- transcriptional processing

21 Enormous amount of information in RNA and proteins regulate cellular fate DNA mRNA protein ~20,000 genes ~1,000,000 proteins

22 Gene expression: Running the program DNA mRNA protein Promoter: Controls transcription of DNA to RNA pX Non-coding RNA: Controls processing of mRNA into proteins Proteins: Provide structure, energy production, regulation, define various cell types

23 Genetically identical but different Protein N ………………………… Protein 1 ………………………… Heart muscle cells Brain cellsBlood cells pX

24 Protein N ………………………… Protein 1 ………………………… Heart muscle cells Brain cellsBlood cells pX Levels of gene expression define cell types < > ~

25 Heart muscle cells Brain cellsBlood cells Levels of gene expression define cell types < > ~ Spectrum of fate Levels of expression Protein NProtein 1

26 Synthetic control systems control gene expression to reprogram cell fate Figure adapted from Amabile, G. & A. Meissner (2009) Trends Mol. Med. 15:59.

27 Simple model for proper protein folding Native protein structure goes to lowest energy state, process runs downhill

28 Multi-level control for proper protein folding Native protein structure is metastable, kinetically entrapped, guided to native fold

29 Important molecular control at all three levels DNA mRNA protein Promoter: Controls transcription of DNA to RNA pX Non-coding RNA: Controls processing of mRNA into proteins Proteins: Provide structure, energy production, regulation, define various cell types

30 MoleculesNetworksCellsTissuesSystemsOrganism Layers of design Environment & society Input: Initial conditions Output: Fate

31 No gene is an island

32 Fast negative regulation Fast positive regulation Transcriptional regulation A systems view of the yeast mating pathway: model cancer pathway Figure courtesy of D.Endy. 2006

33 MAPK pathways: regulators of cell fate Transmembrane receptor MAPKKK MAPKK MAPK Extracellular signal Pathway response Mating Proliferation Differentiation Development Inflammation Apoptosis Development Yeast Mammalian PheromoneGrowth factors, cytokines, cell stress Fus3Erk1/2JNK p38

34 Implications in disease and therapeutics Stem CellsCancer Hanahan, D. and R.A. Weinberg, The hallmarks of cancer. Cell, (1): p

35 Proliferation Differentiation Adapted from Santos, SD et al. Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate. Nat Cell Biol 2007 Proliferation EGF NGF - Differentiation + Signaling = Biology’s Morse code

36 Proliferation Differentiation Adapted from Santos, SD et al. Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate. Nat Cell Biol 2007 Proliferation EGF NGF - Differentiation + Complex signal processing used to direct cell fate

37 MoleculesNetworksCellsTissuesSystemsOrganism Environment & society Input: Initial conditions Output: Fate Layers of design

38 Life or death in response to pro-death signal is context dependent

39 Coordination of homeostasis in the intestine

40 Coordination of multiple cell types required to prevent megadeath, disaster in the intestine

41 MoleculesNetworksCellsTissuesSystemsOrganism Environment & society Input: Initial conditions Output: Fate Layers of design

42 Stress is translated into changes in hormones, genes, and ultimately cell fate

43 Stress can impair the immune system, brain function

44 Maternal nurturing reduces stress

45 MoleculesNetworksCellsTissuesSystemsOrganism Layers of design Environment & society Input: Initial conditions Output: Fate

46 MoleculesNetworksCellsTissuesSystemsOrganism Feedback changes the nature of integrated system Environment & society Input: Initial conditions Output: Fate

47 MoleculesNetworksCellsTissuesSystemsOrganism Even with feedback this is still a biochemical machine Environment & society Input: Initial conditions Output: Fate

48 MoleculesNetworksCellsTissuesSystemsOrganism Unless there is a mind and free will Environment & society Input: Initial conditions Output: Fate Mind, Will

49 Modifying fate via behavior

50 MoleculesNetworksCellsTissuesSystemsOrganism Yet, if our hope is in our will, do we have hope? Environment & society Input: Initial conditions Output: Fate Mind, Will

51 For I do not do the good I want to do, but the evil I do not want to do—this I keep on doing. -Romans 7: 19 Hope in free will? Yes and no.

52 MoleculesNetworksCellsTissuesSystemsOrganism God’s intervention, mercy and grace give hope Environment & society Input: Initial conditions Output: Fate Mind, Will God, Holy Spirit, Mercy, Grace

53 MoleculesNetworksCellsTissuesSystemsOrganism God’s intervention, mercy and grace give hope Environment & society Input: Initial conditions Output: Fate Mind, Will God, Holy Spirit, Mercy, Grace God is able and willing to help those who recognize their need And Jesus said to him, “ ‘If You can?’ All things are possible to him who believes.” Immediately, the boy’s father cried out and said, “I do believe; help my unbelief.” -Mark 9:23-24

54 MoleculesNetworksCellsTissuesSystemsOrganism Quick summary: layers of design Environment & society Input: Initial conditions Output: Fate

55 MoleculesNetworksCellsTissuesSystemsOrganism Quick Summary: more than a biochemical machine Environment & society Input: Initial conditions Output: Fate Mind, Will

56 MoleculesNetworksCellsTissuesSystemsOrganism Quick Summary: God designed free will & hope into our very being via our bodies, minds, and the Holy Spirit Environment & society Input: Initial conditions Output: Fate Mind, Will God, Holy Spirit, Mercy, Grace

57 A word of caution… Jesus answered them. “Love the Lord your God with all your heart and with all your soul and with all your mind.’ This is the first and greatest commandment. And the second is like it: ‘Love your neighbor as yourself.’ All the Law and the Prophets hang on these two commandments.” -Matthew 22:37-40

58 Questions for reflection 1.Is the material world enough to account for the design I see in nature? If the material world is all that there is, am I satisfied knowing I am a biochemical machine? 2.For those that embrace the potential of life beyond materialism, is the will enough? Is the will enough to make you the person you should be? 3.Evidence for a personal, loving, merciful God? 4.In light of how important the mind is to knowing God and how important social interactions can be on influencing the brain, am I acting as lovingly as I can? Am I being as kind? As gracious? Am I forgiving? Am I avoiding anger, resolving conflict? 5.How will you allow the Holy Spirit to transform you? 6.How will you build your faith today?

59 Questions…?


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