8lol 203 : Molecular uevelopmenLal

geneLlcs
Wllllam 8endena
8oom 2443
8losclences complex
613-333-6121
wllllam.bendena[queensu.ca
Willy
Shoemaker
Wilt
Chamberlin
Figure 1.1
Gregor Mendel -1865
Principles of Segregation
No one cared!
Hugo
de Vries
Carl
Correns
35 yrs later
Eric van Tsechermak
35 Years Later: Mendel`s experiments confirmed
1900-1925 devoted to proving chromosomes
were hereditary material
46 human
chromosomes
1925-1953 -Structure of DNA
James
Watson
Francis
Crick
James Watson F rancis Crick
Rosalind
Franklin
1950-1975 :
Learning how
DNA is read!

Replication
Transcription
Translation

Developing
Tools!

!"#$%&' )*+,&
"-./0102.34
RNA
reverse transcribed to
make DNA-
trancriptional
complexes will take
DNA and make RNA
RNA has an enzymatic
function
3 separate RNA
polymerases
that make RNA
There are exons and
introns, introns
interrupt the coding region
Primers are always
necessary
Late 1980`s Projecting strategies!
all the letters .
freely available to
everyone in every
country!
Automated Colony Picker -160,000 samples/day
New technology had to be developed!
Automated sequencing facility
7 million letters of
sequence/day
~4000 letters
worldwide/second
January 2005
July 2005
Dec 2005
April 2007
5610 78 799: 5;16;<= >98 79>9
What has
the sequence
taught us?
CeneLlc screenlng +
Sequenclng Loo slow
and expenslve!
8affled by fallure Lo uncover
geneLlc varlanLs
ComplexlLy greaLer
Lhan expecLed!
lnformaLlon
Cverload!
Lmerglng 1echnologles
SynLheLlc 8lology
ConsLrucLlon of unA Lo bulld organlsms LhaL
can perform Lasks
- uevelop new blofuels
- urug producLlon
- LnvlronmenLal cleanup
Bacteria that can break down stuff and for
oil
And man made life
Artificial life, the stuff of dreams and nightmares, has arrived
May 20th 2010
Craig ventor made a new organism by putting in man made DNA into an old
organism

lLs an 8nA WC8Lu
8nA lunC1lCnS AS An LnZ?ML
8l8CZ?MLS

1om Cech- noble rlze 1989
8nAl (double-sLranded 8nA)

ds8nA lnhlblLs Lhe gene Lo whlch lL
ls made- degradaLlon and
block!
Andrew llre
nobel rlze 2006
discvered a RNA that destroyed itself and cleav itself and it was completely
new
Mlcro 8nAs
ShorL 8nAs have emerged as a new means of
dlagnoslng and LreaLlng dlsease
Mlcro8nA-
a) block LranslaLlon of m8nA lnLo proLeln
b) lnlLlaLe breakdown of normal m8nA
- Some up or down regulaLe a slngle gene
- CLhers regulaLe mulLlple gene neLworks

RNA is made that doesnt code for protein and people did not know
this

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!"#$%&, 2 SepLember 2010
mlcro8nA-21 (ml8-21) ls overexpressed ln mosL Lypes of human cancer, buL no experlmenLs
have demonsLraLed a causal role for Lhls mlcro8nA ln Lumourlgenesls. Slack and colleagues
have shown '( *'*+ LhaL ml8-21 ls one of a few slngle oncogenes capable of lnlLlaLlng and
malnLalnlng a mallgnanL phenoLype by lLself. Mlce LhaL condlLlonally expressed ml8-21
developed haemaLologlcal mallgnancles LhaL regressed when ml8-21 overexpresslon was
swlLched off. 1hese flndlngs lndlcaLe LhaL pharmacologlcal lnhlblLlon of ml8-21 mlghL help
LreaL many Lypes of human cancers.
Small RNA- 21 nucleotides and it replicates a lot so you get tumor but if you can shut off the microRNA then you can stop the tumour
lmplanLable sensors
C3.012.424 +.D0 EF.04 E;F40 ,0?@<.04
Sclenceually (CcL. 16, 2009) 8y dlrecLly manlpulaLlng Lhe acLlvlLy of
lndlvldual neurons, sclenLlsLs have glven flles memorles of a bad
experlence Lhey never really had, accordlng Lo a reporL ln Lhe CcLober
16Lh lssue of Lhe [ournal ,&--.
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,643F0 ,@D0?012 .1 ,.30
Sclenceually (Sep. 27, 2010) 8esearchers aL SLanford unlverslLy were
able Lo use llghL Lo lnduce normal paLLerns of muscle conLracLlon, ln a
sLudy lnvolvlng bloenglneered mlce whose nerve-cell surfaces are coaLed
wlLh speclal llghL-senslLlve proLelns.
1he new approach allows sclenLlsLs Lo more accuraLely reproduce muscle
flrlng order, maklng lL a valuable research Lool. 1he lnvesLlgaLors, from
SLanford's Schools of Medlclne and of Lnglneerlng, also belleve Lhls Lechnlque
could someday spawn pracLlcal appllcaLlons, from resLorlng movemenL Lo
llmbs paralyzed by sLroke or splnal-cord or braln ln[ury Lo counLerlng
spasLlclLy caused by cerebral palsy.


Optogenetics
Channel rhodopsin 2
(green algae)

-activated by blue light
-causes action potentials

-depolorization-activates
release of neurotransmitter
at synapse between neurons


Halo-rhodopsin
Natronomonas
pharaonis (NpHR)
-generates a chloride flux
when activated by yellow light

-causes hyperpolarization thus
preventing action potentials.
geneLlcally englneered "llghL swlLch," whlch
leLs sclenLlsLs Lurn selecLed parLs of Lhe braln
on and off, may help lmprove LreaLmenLs for
depresslon and oLher dlsorders.
1he flrsL examples of unA nanoLubes LhaL encapsulaLe and load cargo
, and Lhen release lL rapldly and compleLely when a speclflc exLernal unA sLrand ls added.
Cne of Lhese unA sLrucLures ls only a few nanomeLres wlde buL can be exLremely long,
abouL 20,000 nanomeLres. (A nanomeLre ls one-10,000Lh Lhe dlameLer of a human halr.)
nAnC1LCPnCLCC?
&-<.F 79>98 ,3+.FF K1.D0<4.2=
oLenLlal for drug dellvery
#;1@G0;F.1/
1lny flbers wlll save llves by sLopplng bleedlng and aldlng recovery from braln ln[ury

new compound LhaL rapldly forms a LransparenL, nanoflber-rlch meshwork (self-
assembllng pepLlde) LhaL sLops bleedlng lnsLanLly, allows wounds Lo begln heallng
qulckly, promoLes Llssue regeneraLlon, and breaks down harmlessly wlLhln Lhe
body. 1he LransparenL, fluld maLerlal can be easlly applled Lo weL or dry surfaces.
Surgery can be performed Lhrough lL, enabllng fasLer, more accuraLe, and safer
operaLlons. 1hlrd-parLy LesLlng shows LhaL Lhe maLerlal ls non-Loxlc and safe Lo
use lnLernally and exLernally. Moreover, lL does noL requlre removal, because lLs
breakdown producLs can be used by cells ln Lhe heallng process.
SLops bleedlng ln
13 seconds
SLem cells