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Unraveling the Complexity of Human Development Through Gene Expression Analysis

Explore the intricate course of human development over time and space, guided by patterned gene expression. Delve into the challenges faced in understanding the fate of cells, intrinsic versus extrinsic control, genetic manipulation, and the complexity of the human genome. Simplification strategies shed light on complex biological processes. Discover the regulated differentiation in organisms such as Bacillus subtilis and Anabaena, and how gene expression control influences development outcomes.

thomaslwilliams
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Unraveling the Complexity of Human Development Through Gene Expression Analysis

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  1. The Course of Development

  2. The Course of Development Time Events

  3. The Course of Development Time Events

  4. The Course of Development Time Events in time

  5. The Course of Development Time Events in time

  6. The Course of Development Time Events in time and space . . .

  7. The Course of Development Time Events in time and space . . .

  8. The Course of Development Time Events in time and space . . .

  9. The Course of Development Events in time and space . . . . . . driven by patterned gene expression

  10. The Course of Development Understanding Human Development Events in time and space . . . . . . driven by patterned gene expression

  11. The Course of Development Understanding Human Development

  12. The Course of Development Understanding Human Development

  13. The Course of Development Understanding Human Development The fate of cells Intrinsic control? patterned in time and space Extrinsic control?

  14. Understanding Human Development Why so difficult? Process 9 mo – 20 yrs Generation 20 yrs Genetic recombination Uncontrolled Genetic manipulation Difficult / Impossible Genome size ~3 billion nucleotides Development Complex How to attack a problem that’s too complex?

  15. How to Attack a Complex Problem Probability of getting a full house?

  16. How to Attack a Complex Problem Probability of getting a pair?

  17. How to Attack a Complex Problem 1 · 3/51 Probability of getting a pair in 2 cards?

  18. Simplification can help in understanding complexity

  19. Understanding Human Development Why so difficult? Process 9 mo – 20 yrs Generation 20 yrs Genetic recombination Uncontrolled Genetic manipulation Difficult / Impossible Genome size ~3 billion nucleotides Development Complex

  20. Understanding Fly Development Still difficult Process 9 mo – 20 yrs ~8 days Generation 20 yrs ~14 days Genetic recombination Uncontrolled Controlled Genetic manipulation Difficult / Impossible Difficult Genome size ~3 billion nucleotides ~170 million nucleotides Development Complex Complex How to simplify further?

  21. Understanding Any Development What do we want in a model organism? Process ~8 days Hours Generation ~14 days Hours Genetic recombination Controlled Genetic manipulation Difficult Easy Genome size ~170 million nucleotides Few million nucleotides Development Complex Single phenomenon Does such an organism exist?

  22. Bacteria E. coli . . . but no development

  23. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation

  24. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation

  25. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation

  26. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation

  27. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation Development in time and space

  28. heterocysts sucrose Heterocyst differentiation by Anabaena Free-living Nostoc N2 CO2 O2 Matveyev and Elhai (unpublished)

  29. heterocysts sucrose NH3 Heterocyst differentiation by Anabaena Free-living Nostoc NH3 N2 O2 CO2 Matveyev and Elhai (unpublished)

  30. Time after nitrogen removal 0 h 3 h 6 h 9 h 12 h 18 h Heterocyst differentiation by Anabaena AnabaenaSpatially regulated differentiation N2 fixation

  31. Time after nitrogen removal 0 h 3 h 6 h 9 h 12 h 18 h N2 fixation Heterocyst differentiation by Anabaena AnabaenaSpatially regulated differentiation

  32. Time after nitrogen removal 0 h 3 h 6 h 9 h 12 h 18 h N2 fixation Heterocyst differentiation by Anabaena AnabaenaSpatially regulated differentiation Development of pattern Mark Hill, University of New South Wales http://anatomy.med.unsw.edu.au/cbl/embryo/Notes/skmus7.htm

  33. Fruiting body formation by Myxococcus Herd motility

  34. Fruiting body formation by Myxococcus Herd development

  35. Fruiting body formation by Myxococcus Extrinsic control over development

  36. Cell cycle of Caulobacter Caulobacter crescentusCell cycle-regulated differentiation swarmercell

  37. Cell cycle of Caulobacter Caulobacter crescentusCell cycle-regulated differentiation stalkcell swarmercell

  38. Cell cycle of Caulobacter Caulobacter crescentusCell cycle-regulated differentiation swarmercell stalkcell

  39. Cell cycle of Caulobacter Caulobacter crescentusCell cycle-regulated differentiation Intrinsic control over development

  40. Bacterial Development End result... much simpler Anabaena heterocysts Bacillus sporulation Caulobacter cell cycle Myxobacteria fruiting

  41. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation Control of initiation selective gene expression ? How to makethe decision?

  42. Bacterial regulation of gene expression Transcriptional factors RNAPol DNA P RNA protein

  43. signal Bacterial regulation of gene expression Transcriptional factors DNA binding protein RNAPol No stimulus Stimulus DNA Binding site P No RNA

  44. signal Bacterial regulation of gene expression Transcriptional factors DNA binding protein RNAPol No stimulus Stimulus DNA Binding site P No RNA

  45. signal RNA protein Bacterial regulation of gene expression Transcriptional factors RNAPol Spo0A No stimulus Stimulus DNA Binding site P

  46. K F B A ATP Spo genes P P P P P P K F B A ADP Spo genes spo0A spo0F spo0B kinA Sporulation by Bacillus subtilis Control of initiation selective gene expression Why??? Spores

  47. Cell density Control by phosphatases K F B A ATP Spo genes P P P P P P P P K F B A ADP Spo genes kinA spo0A spo0B spo0F Sporulation by Bacillus subtilis Phosphorelay as an integration processing device ? Spores - Cell cycle- DNA damage- Nutrient status

  48. Sporulation by Bacillus subtilis Control of initiation of development • Integration of signals through signal transduction • Centers on phosphorylation of master protein • DNA binding protein regulates transcription

  49. Fore-spore Mother cell Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation Control of timing by selective gene expression Set 0 Set II Set V Set IV Set III

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