Download
1 / 58
580 likes | 752 Vues
Eye as an evolutionary challenge. To suppose that the eye, with all its inimitable contrivances , could have been formed by natural selection, seems, I freely confess, absurd in the highest possible degree. Yet reason tells me, C. Darwin, The Origin of Species:. Darwin goes on to describe h
E N D
1. Modeling signal transduction In this lecture i want to take a small bite at understanding how the eye works on the molecular level.In this lecture i want to take a small bite at understanding how the eye works on the molecular level.
2. Eye as an evolutionary challenge A fact recognaized by Darwin, who wrote
Lophotrochozoa (Molluscs); Ecdysozoa (Athropods);
Cnidaria (Jelly fish); Deuterostomia (Vertebrates);
Despite great anatomical similarity of vertebrate and sephalopod (mollusk) eyes in the former they develop as an outfrowth of the brain in the latter as a peripheral ectoderm. In cnidarian jellyfish, there is a sophisticated eye
Cornea/lens/retina, but NO BRAIN at all.
There are many fundamantal questions. E.g. there is a debate going on on whether eyes in different phyla have evolved
From a common precursor or by convergent evolution. I will not get even close to answering these grand questions. I just want to bring them to your attention hoping that one of you will pick up the challenge and in a few years time enlighten us all. It is not possible to answer the question without getting intimately acquainted with the system.
So i will spend the next hour telling you about photo-transduction in vertebrates and insects on the molecular level.A fact recognaized by Darwin, who wrote
Lophotrochozoa (Molluscs); Ecdysozoa (Athropods);
Cnidaria (Jelly fish); Deuterostomia (Vertebrates);
Despite great anatomical similarity of vertebrate and sephalopod (mollusk) eyes in the former they develop as an outfrowth of the brain in the latter as a peripheral ectoderm. In cnidarian jellyfish, there is a sophisticated eye
Cornea/lens/retina, but NO BRAIN at all.
There are many fundamantal questions. E.g. there is a debate going on on whether eyes in different phyla have evolved
From a common precursor or by convergent evolution. I will not get even close to answering these grand questions. I just want to bring them to your attention hoping that one of you will pick up the challenge and in a few years time enlighten us all. It is not possible to answer the question without getting intimately acquainted with the system.
So i will spend the next hour telling you about photo-transduction in vertebrates and insects on the molecular level.
3. Eyes are present in most metazoan phyla: how did they evolve? Now. Everybody (at least most metazoans) got eyes. Trilobites had compound eyes very reminiscent of those of insects.
Even scallops apparently got some sort of a primitive eye, and octopus has a sophisticated camera eye very remiscient of vertebrate except theres no plausible common ancestor. Understanding eye evolution is a major challenge.Now. Everybody (at least most metazoans) got eyes. Trilobites had compound eyes very reminiscent of those of insects.
Even scallops apparently got some sort of a primitive eye, and octopus has a sophisticated camera eye very remiscient of vertebrate except theres no plausible common ancestor. Understanding eye evolution is a major challenge.
4. The grand challenge:
5. More broadly: Molecular pathway(s) of phototransduction are similar to many other signaling pathways:
olfaction, taste, etc
Comparative Systems Biology
6. Modeling molecular mechanisms of photo-transduction
7. Vertebrate Rods and Cones
8. Vertebrate photoreceptor cell
9. Intracellular Voltage in Rods and Cones
10. Measuring currents
11. Patch clamp
12. Single Photon Response
13. Patch clamp recordings
14. Electrophysiology of Rods
15. Light detector protein: Rhodopsin
16. cis/trans retinal transition
17. Light-induced conformational transition
18. Rhodopsin is a G-Protein coupled receptor
20. Rhodopsin is a G-Protein coupled receptor
21. G- proteins
22. Steps in activation
24. Effector
25. Where did cGMP come from?
26. G Protein Effectors Include
27. Shut-off
28. Rhodopsin inactivation
29. Transducin is inactivated by the a intrinsic GTPase activity which hydrolyzes GTP to GDP
31. Recovery to the resting state requires resynthesis of the cGMP that had been lost to hydrolysis.
32. Ca- the second 2nd messenger
33. Negative feedback
34. Signaling cascade
35. Phototransduction Cascade as an enzymatic amplifier
36. Olfaction:
37. Olfactory receptor cascade
38. Invertebrate Phototransduction Cascade
39. Enzymatic amplifier modules This cascade picture patently omitted recover steps. When we remember those the amplifier modules start to look like this.This cascade picture patently omitted recover steps. When we remember those the amplifier modules start to look like this.
40. More examples of amp modules GEF guanine nucleotide exchange factor and GAP GTPase activating proteinGEF guanine nucleotide exchange factor and GAP GTPase activating protein
41. General push-pull amplifier circuit Homework: derive this using Michaelis-Menten. Of course there are all sorts of saturation effectsHomework: derive this using Michaelis-Menten. Of course there are all sorts of saturation effects
42. Amplifier gain and time constant
43. Linear analysis of vertebrate phototransduction
44. Linear analysis of the cascade
45. Hard and Soft parameters
46. General behavior Exlain what happens if tau is very smallExlain what happens if tau is very small
47. Case of feedback
48. Consequences of negative feedback
49. Signal and Noise: How much gain is enough?
50. Reaction shot noise
51. Channel opening noise
52. cGMP fluctuations
53. Locality of single photon response
54. Single photon response variability
55. What is the largest source of response variability?
56. Multistep deactivation of Rh*
57. Meta-Rhodopsin shut-off:
58. Summary:
59. Acknowledgements
