Post on 21-Dec-2015
9. Ion flow9. Ion flow
Fain Chapter 3 part 19/30/09
Homework - rhodopsin seqsHomework - rhodopsin seqs
Human_rho MNGTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYChimp_rho MNGTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYDog_rho MNGTEGPNFYVPFSNKTGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYMouse_rho MNGTEGPNFYVPFSNVTGVVRSPFEQPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYRat_rho MNGTEGPNFYVPFSNITGVVRSPFEQPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYCow_rho MNGTEGPNFYVPFSNKTGVVRSPFEAPQYYLAEPWQFSMLAAYMFLLIMLGFPINFLTLYZfish_rho MNGTEGPAFYVPMSNATGVVRSPYEYPQYYLVAPWAYGFVAAYMFFLIITGFPVNFLTLYChick_rho MNGTEGINFYVPMSNKTGVVRSPFEYPQYYLAEPWKYRLVCCYIFFLISTGLPINLLTLL ****** ****:** *******:* *****. ** : ::..*:*:** *:*:*:*** 23 variable Human_rho VTVQHKKLRTPLNYILLNLAVADLFMVLGGFTSTLYTSLHGYFVFGPTGCNLEGFFATLGChimp_rho VTVQHKKLRTPLNYILLNLAVADLFMVLGGFTSTLYTSLHGYFVFGPTGCNLEGFFATLGDog_rho VTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTLYTSLHGYFVFGPTGCNVEGFFATLGMouse_rho VTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTLYTSLHGYFVFGPTGCNLEGFFATLGRat_rho VTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTLYTSLHGYFVFGPTGCNLEGFFATLGCow_rho VTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTLYTSLHGYFVFGPTGCNLEGFFATLGZfish_rho VTIEHKKLRTPLNYILLNLAIADLFMVFGGFTTTMYTSLHGYFVFGRLGCNLEGFFATLGChick_rho VTFKHKKLRQPLNYILVNLAVADLFMACFGFTVTFYTAWNGYFVFGPVGCAVEGFFATLG **.:***** ******:***:*****. *** *:**: :****** ** :******** 17
Human_rho GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLAGWS----Chimp_rho GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLAGWS----Dog_rho GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLAGWSSLLSMouse_rho GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVVFTWIMALACAAPPLVGWS----Rat_rho GEIGLWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLVGWS----Cow_rho GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLVGWS----Zfish_rho GEMGLKSLVVLAIERWMVVCKPVSNFRFGENHAIMGVAFTWVMACSCAVPPLVGWS----Chick_rho GQVALWSLVVLAIERYIVVCKPMGNFRFSATHAMMGIAFTWVMAFSCAAPPLFGWS---- *::.* *********::*****:.****. .**:**:.***:** :**.*** *** 23
Human_rho ------RYIPEGLQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIIIFFCYGQLVFTVChimp_rho ------RYIPEGLQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIIIFFCYGQLVFTVDog_rho HSPLVLRYIPEGMQCSCGIDYYTLKPEINNESFVIYMFVVHFAIPMIVIFFCYGQLVFTVMouse_rho ------RYIPEGMQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIVIFFCYGQLVFTVRat_rho ------RYIPEGMQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIVIFFCYGQLVFTVCow_rho ------RYIPEGMQCSCGIDYYTPHEETNNESFVIYMFVVHFIIPLIVIFFCYGQLVFTVZfish_rho ------RYIPEGMQCSCGVDYYTRTPGVNNESFVIYMFIVHFFIPLIVIFFCYGRLVCTVChick_rho ------RYMPEGMQCSCGPDYYTHNPDYHNESYVLYMFVIHFIIPVVVIFFSYGRLICKV **:***:***** **** :***:*:***::** **:::***.**:*: .* 28
Human_rho KEAAAQQQESATTQKAEKEVTRMVIIMVIAFLICWVPYASVAFYIFTHQGSNFGPIFMTIChimp_rho KEAAAQQQESATTQKAEKEVTRMVIIMVIAFLICWVPYASVAFYIFTHQGSNFGPIFMTIDog_rho KEAAAQQQESATTQKAEKEVTRMVIIMVIAFLICWVPYASVAFYIFTHQGSDFGPIFMTLMouse_rho KEAAAQQQESATTQKAEKEVTRMVIIMVIFFLICWLPYASVAFYIFTHQGSNFGPIFMTLRat_rho KEAAAQQQESATTQKAEKEVTRMVIIMVIFFLICWLPYASVAMYIFTHQGSNFGPIFMTLCow_rho KEAAAQQQESATTQKAEKEVTRMVIIMVIAFLICWLPYAGVAFYIFTHQGSDFGPIFMTIZfish_rho KEAARQQQESETTQRAEREVTRMVIIMVIAFLICWLPYAGVAWYIFTHQGSEFGPVFMTLChick_rho REAAAQQQESATTQKAEKEVTRMVILMVLGFMLAWTPYAVVAFWIFTNKGADFTATLMAV :*** ***** ***:**:*******:**: *::.* *** ** :***::*::* . :*:: 25
Human_rho PAFFAKSAAIYNPVIYIMMNKQFRNCMLTTICCGKNPLGDDE--ASATVSKTETSQVAPAChimp_rho PAFFAKSAAIYNPVIYIMMNKQFRNCMLTTICCGKNPLGDDE--ASATVSKTETSQVAPADog_rho PAFFAKSSSIYNPVIYIMMNKQFRNCMITTLCCGKNPLGDDE--ASASASKTETSQVAPAMouse_rho PAFFAKSSSIYNPVIYIMLNKQFRNCMLTTLCCGKNPLGDDD--ASATASKTETSQVAPARat_rho PAFFAKTASIYNPIIYIMMNKQFRNCMLTTLCCGKNPLGDDE--ASATASKTETSQVAPACow_rho PAFFAKTSAVYNPVIYIMMNKQFRNCMVTTLCCGKNPLGDDE--ASTTVSKTETSQVAPAZfish_rho PAFFAKTSAVYNPCIYICMNKQFRHCMITTLCCGKNPFEEEEG-ASTTASKTEASSVSSSChick_rho PAFFSKSSSLYNPIIYVLMNKQFRNCMITTICCGKNPFGDEDVSSTVSQSKTEVSSVSSS ****:*::::*** **: :*****:**:**:******: ::: ::.: ****.*.*:.: 29
Human_rho -----Chimp_rho -----Dog_rho -----Mouse_rho -----Rat_rho -----Cow_rho -----Zfish_rho SVSPAChick_rho QVSPA 5
Total sites = 6*60 + 5 -= 365
Variable = 150
Fixed = 215 / 365 = 58.9%
Protein interactionsProtein interactions
Rhodopsin
GNAT1
GNB1
GNGT1
G protein kinaseArrestin
Protdist - pairwise distancesProtdist - pairwise distances
Distance = difference btn 2 sequences = 1 - fraction of fixed sites
HW - dist matrix for RhoHW - dist matrix for Rho
8
Human_rho 0.00000 0.00001 0.04769 0.05420 0.05186 0.07040 0.242057 0.38324
Chimp_rho 0.00001 0.00000 0.04769 0.05420 0.05186 0.07040 0.24206 0.38324
Dog_rho 0.04769 0.04769 0.00000 0.04525 0.04846 0.06124 0.22672 0.34926
Mouse_rho 0.05419 0.05420 0.04525 0.00000 0.02969 0.07087 0.23692 0.38622
Rat_rho 0.05185 0.05185 0.04846 0.02969 0.00000 0.06790 0.22196 0.39169
Cow_rho 0.07040 0.07040 0.06124 0.07087 0.06790 0.00000 0.21113 0.37531
Zfish_rho 0.24206 0.24206 0.22672 0.23692 0.22196 0.21113 0.00000 0.41065
Chick_rho 0.38324 0.38324 0.34926 0.38622 0.39170 0.37531 0.41065 0.00000
Homework - dist matrix for Homework - dist matrix for RhoRho
8 Human Chimp Dog Mouse Rat Cow Zfish Chick
Human_rho 0.00000 0.00001 0.04769 0.05420 0.05186 0.07040 0.242057 0.38324
Chimp_rho 0.00001 0.00000 0.04769 0.05420 0.05186 0.07040 0.24206 0.38324
Dog_rho 0.04769 0.04769 0.00000 0.04525 0.04846 0.06124 0.22672 0.34926
Mouse_rho 0.05419 0.05420 0.04525 0.00000 0.02969 0.07087 0.23692 0.38622
Rat_rho 0.05185 0.05185 0.04846 0.02969 0.00000 0.06790 0.22196 0.39169
Cow_rho 0.07040 0.07040 0.06124 0.07087 0.06790 0.00000 0.21113 0.37531
Zfish_rho 0.24206 0.24206 0.22672 0.23692 0.22196 0.21113 0.00000 0.41065
Chick_rho 0.38324 0.38324 0.34926 0.38622 0.39170 0.37531 0.41065 0.00000
Distances are fraction of sites which differ
Small distance means small difference = high similarity
Trifurcating tree
Can reroot
Zebrafish makes the most sense as the root.
Is this the tree you expect?
ParsimonyParsimonyTrees joined in different ways are just as likely based on # of changes
Distance and ML trees are similar Distance and ML trees are similar but not identicalbut not identical
Distance
Max likelihood
oooooooooooooooooooooooooooooooooooooooooooooooooooooooooo --- PhyML v3.0 ---
A simple, fast, and accurate algorithm to estimate large phylogenies
by maximum likelihood Stephane Guindon & Olivier Gascuel
http://atgc.lirmm.fr/phyml
Copyright CNRS - Universite Montpellier II
ooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo. Sequence file : Rho.phylipi. Data set : #1. Tree search : NNIs. Initial tree : BIONJ. Model of amino acids substitution : LG. Number of taxa : 8. Log-likelihood : -2100.30553. Discrete gamma model : No. Time used 0h0m5s oooooooooooooooooooooooooooooooooooooooooooooooooooooooooooLog-likelihood is a statistic which tells you how
good the tree is : more negative is better
What did we learn from all What did we learn from all this?this?
Distance is fast Parsimony gives us too many trees
and no similarity info ML is best - provides confidence
on resultsBut it can take forever
Human_rho MNGTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYChimp_rho MNGTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYDog_rho MNGTEGPNFYVPFSNKTGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYMouse_rho MNGTEGPNFYVPFSNVTGVVRSPFEQPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYRat_rho MNGTEGPNFYVPFSNITGVVRSPFEQPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYCow_rho MNGTEGPNFYVPFSNKTGVVRSPFEAPQYYLAEPWQFSMLAAYMFLLIMLGFPINFLTLYZfish_rho MNGTEGPAFYVPMSNATGVVRSPYEYPQYYLVAPWAYGFVAAYMFFLIITGFPVNFLTLYChick_rho MNGTEGINFYVPMSNKTGVVRSPFEYPQYYLAEPWKYRLVCCYIFFLISTGLPINLLTLL ****** ****:** *******:* *****. ** : ::..*:*:** *:*:*:*** 23 variable Human_rho VTVQHKKLRTPLNYILLNLAVADLFMVLGGFTSTLYTSLHGYFVFGPTGCNLEGFFATLGChimp_rho VTVQHKKLRTPLNYILLNLAVADLFMVLGGFTSTLYTSLHGYFVFGPTGCNLEGFFATLGDog_rho VTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTLYTSLHGYFVFGPTGCNVEGFFATLGMouse_rho VTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTLYTSLHGYFVFGPTGCNLEGFFATLGRat_rho VTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTLYTSLHGYFVFGPTGCNLEGFFATLGCow_rho VTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTLYTSLHGYFVFGPTGCNLEGFFATLGZfish_rho VTIEHKKLRTPLNYILLNLAIADLFMVFGGFTTTMYTSLHGYFVFGRLGCNLEGFFATLGChick_rho VTFKHKKLRQPLNYILVNLAVADLFMACFGFTVTFYTAWNGYFVFGPVGCAVEGFFATLG **.:***** ******:***:*****. *** *:**: :****** ** :******** 17
Human_rho GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLAGWS----Chimp_rho GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLAGWS----Dog_rho GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLAGWSSLLSMouse_rho GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVVFTWIMALACAAPPLVGWS----Rat_rho GEIGLWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLVGWS----Cow_rho GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLVGWS----Zfish_rho GEMGLKSLVVLAIERWMVVCKPVSNFRFGENHAIMGVAFTWVMACSCAVPPLVGWS----Chick_rho GQVALWSLVVLAIERYIVVCKPMGNFRFSATHAMMGIAFTWVMAFSCAAPPLFGWS---- *::.* *********::*****:.****. .**:**:.***:** :**.*** *** 23
Human_rho ------RYIPEGLQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIIIFFCYGQLVFTVChimp_rho ------RYIPEGLQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIIIFFCYGQLVFTVDog_rho HSPLVLRYIPEGMQCSCGIDYYTLKPEINNESFVIYMFVVHFAIPMIVIFFCYGQLVFTVMouse_rho ------RYIPEGMQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIVIFFCYGQLVFTVRat_rho ------RYIPEGMQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIVIFFCYGQLVFTVCow_rho ------RYIPEGMQCSCGIDYYTPHEETNNESFVIYMFVVHFIIPLIVIFFCYGQLVFTVZfish_rho ------RYIPEGMQCSCGVDYYTRTPGVNNESFVIYMFIVHFFIPLIVIFFCYGRLVCTVChick_rho ------RYMPEGMQCSCGPDYYTHNPDYHNESYVLYMFVIHFIIPVVVIFFSYGRLICKV **:***:***** **** :***:*:***::** **:::***.**:*: .* 28
Funky dog sequence- predicted from genome
GNB (GNB ( subunit of G protein transducin) subunit of G protein transducin)
Rod
Cone
Cone cladeCone clade
Rod cladeRod cladeA
B
Key steps of sensory Key steps of sensory transductiontransduction
1. Stimulus is received2. Changes confirmation of receptor
molecule3. Causes change in membrane
potential4. Changes neural output
Change in membrane Change in membrane potentialpotential
To change membrane potential, need to get ions to flow
Two ways for ions to flowIon channel
Passive flow - diffusionIon pump
Active flow - uses energy
QuestionsQuestions
1. How do ion channels obtain specificity?
2. How do ion pumps differ?3. How are membrane potential and
ion concentration related?What does that tell us about
mechanism?
Ion channelIon channel
Integral to membraneEmbedded in hydrophobic
environmentTraverses one side of membrane to the
other Comprised of several protein
subunitsHomodimer - same subunitsHeterodimer - different subunits
Ion channelIon channel
Has a special region that forms a pore or channel
Conducts one type of ionSize specificIon flow through channel is very fast
Pore is gatedCan be either closed or openConformational change - move AA
which normally occlude opening
Shaker potassium channelShaker potassium channel
Discovered in Drosophila melanogasterShake legs when
anaesthetized with ether
Identified mutation in gene for subunit of an ion channelSelective for K+
Papazain et al 1987Temple et al 1987
subunit of channelsubunit of channel
Fain fig 3.1a
Pore regionPore region
Fain 3.1b
How ion channels workHow ion channels work
Nobel prize for Chemistry 2003Roderick Mackinnon, Rockefeller Univ
X ray crystal structure of X ray crystal structure of bacterial channelbacterial channel
K+ channel from Streptomyces lividans (simple channel)
Channel has 6 TM + 1 P Channel has 6 TM + 1 P regionregion
4 subunitsper channel
P region is highly conservedP region is highly conserved
Conformational change when Conformational change when channel openschannel opens
Voltage gated
Pore regions are right in the Pore regions are right in the middle of the channelmiddle of the channel
KK++ enters as hydrated ion enters as hydrated ion
KK++ sheds water and sheds water and coordinates with COOcoordinates with COO--
groupsgroups
4 possible binding sites
Selectivity: KSelectivity: K++ is necessary is necessary for stable channel structurefor stable channel structure
Selectivity for K+ / Na+ = 10,000
High Naconcentration
4 sites - 2 ions bind4 sites - 2 ions bind
Channels are gatedChannels are gated
Voltage gated - ion specificNa+ K+ Ca+2 Cl-
Ca+2 activated Cyclic nucleotide gated - cAMP,
cGMP Ligand gated - acetylcholine,
glutamate Light gated Stretch gated
Voltage gating - charged AA Voltage gating - charged AA in membrane movein membrane move
Fig 3.3a
Types of channelsTypes of channels
Ionotropic Signal from outside cellVoltage, stretch, ligand
MetabotropicSignal from inside cellLigandModifier (Ca)
Fig 3.3
Voltage gated
Ligand gated - extracellular
cGMP - intracellular
Ionotropic channelsIonotropic channels
Channel is the receptorDetects deformation or change in
pressure Important in
Mechanoreceptors of skinStretch receptors in muscleHair cells in vestibular system and ear
Stretch activated channelsStretch activated channels
Fig 3.4
0
Patch of membrane also Patch of membrane also responds to pressureresponds to pressure
Ionotropic - doesn’t need inside of cell to respond so not metabotropic
Fain 3.4b
Channels Channels
Channels allow ions to move down concentration gradient
Channels vs pumpsChannels vs pumps
Ion pumps move ions against concentration gradients - use energy
Ion pumps - NaIon pumps - Na++/K/K++ ATPase ATPase
Fain 3.7a
Two subunits - subunit binds ions
Sodium pumpSodium pump
Cell interior
Ion pumps - NaIon pumps - Na++/K/K++ ATPase ATPase
3Na+
Fain 3.7b
Ion pumps - NaIon pumps - Na++/K/K++ ATPase ATPase
3Na+ pumped out
2K+ pumped in
Fain 3.7b
Ion pump creates a concentration Ion pump creates a concentration gradient across cell membranegradient across cell membrane
Na/K ATPase
Outside cell Inside cell
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
K+
K+
K+
K+
K+
K+
K+
K+
K+
K+
K+
K+
K+
Cl-
Cl-
Cl-
Cl-
Cl-
Cl-
Cl-
Cl-
Cl-
Cl-
Cl-
Cl-
K+
32
Membrane potentialsMembrane potentials
Ion flow sets up concentration gradients
Ion concentrations determine voltage or potential across cell membrane
Changes in membrane potential are signals produced by sensory cells
Communicated to central nervous system (Action potentials)
Ion pump creates a concentration Ion pump creates a concentration gradient across cell membranegradient across cell membrane
Na/K ATPase
Outside cell Inside cell
Na+
K+
Cl-
10-20 mM
5-10 mM
120-140 mM
Na+
K+
Cl-
141 mM
124 mM
3.3 mM
Membrane potentialMembrane potential
When channels are open, there will be a balance of diffusion and electrostatics
-------
K+ K+ Concentration
Charge
Mass and charge make K+ move in opposite directions
Walther NernstWalther Nernst
Won Nobel prize in chemistry in 1920
Original “Nernst equation” was written for electrochemistry
Personification of Nernst Personification of Nernst equation - students in a equation - students in a
classroomclassroom
Students will move out until Students will move out until same density in and outsame density in and out
If there are a few hot fudge If there are a few hot fudge sundaes…sundaes…
Might get few students coming back in
If there are lots of sundaes…If there are lots of sundaes…
Everyone who wants one will come back in
Nernst equationNernst equation
At equilibrium, can determine membrane potential which offsets ion gradient across membrane
€
Vm =RT
zFlnKoK i
Vm =59mV
zlogKoK i
-------
K+ K+
Vm
Ko - outsideKi - inside
+++++++++
Membrane potential increases till Membrane potential increases till there is equilibriumthere is equilibrium
Outside cell Inside cell
120 mMNa/K ATPase
K+ K+3.3 mM
€
Vm = 59mV (log(3.3
120) = −92mV
-----------
++++++++++
Actual membranes involve transfer Actual membranes involve transfer of several ionsof several ions
Na/K ATPase
Outside cell Inside cell
Na+
K+
Cl-
15 mM
5 mM
120 mM
Na+
K+
Cl-
141 mM
124 mM
3.3 mM
Goldman voltage equation Goldman voltage equation consider multiple ionsconsider multiple ions
For both Na and K
If is ratio of permeabilities: PNa/PK
€
Vm =RT
FlnαNao +KoαNai +K i
€
Vm =RT
FlnPNaNao + PKKoPNaNai + PKK i
For a K selective channel, = 0.02
Membrane potential is less when Membrane potential is less when consider both Naconsider both Na++ and K and K++
Na/K ATPase
Outside cell Inside cell
Na+
K+
15 mM
120 mM
Na+
K+
141 mM
3.3 mM
€
Vm = 59mV ln0.02*141+ 3.3mM
0.02*15 +120mM= −78mV
This is close to actual membrane potential measured in olfactory receptor
Typical cellsTypical cells
Variation in Na permeabilityChanges resting membrane potential
-35 mV to -90 mVAlways negative inside cell
Sometimes need to include Ca+2 or Cl-
Na+/Ca+2 ATPase
Ion channels perturb steady Ion channels perturb steady state membrane potentialstate membrane potential
Opening of channels lets ions flowPositive ions flow in to negative cell :
Na+ Ions in high concentration outside cell
flow in : Na+ Na+ flowing in makes cell less
negativeDepolarizes
Depolarization - become less Depolarization - become less polarized; potential gets polarized; potential gets
smallersmaller
-75mV
-35 mV
stimulus
+ Ion flow into cell
Membrane potential decreases
0 V
Vm
QuestionsQuestions
1. How do ion channels obtain specificity?
2. How do ion pumps differ?3. How are membrane potential and
ion concentration related?What does that tell us about
mechanism?
Next week is Nobel weekNext week is Nobel week
Many Nobel prizes have been awarded for work in sensory systems or genetics
See class web site for links