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8/9/2019 Nobel Laureates in Genetics
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Workshop On Recent Advances In GeneticsWorkshop On Recent Advances In Genetics
GENETICS 2009GENETICS 2009
1919thth
Fer!ar" 2009Fer!ar" 2009
#$ %$ &ati' (niversit"#$ %$ &ati' (niversit"
)o'hap!r)o'hap!r
8/9/2019 Nobel Laureates in Genetics
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Genetic disc veries
enetic disc veries
that have 'ed t the a*ardhat have 'ed t the a*ard
+ the
+ the
N e' &ri,e
e' &ri,e
+ r -edicine.&h"si ' /"
r -edicine.&h"si ' /"
192 200
92 200
8/9/2019 Nobel Laureates in Genetics
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The study of genetics and its role in causinghuman disease is now widely acknowledged asbeing among the most exciting and influentialareas of medical research. Since 1962 when
Francis Crick !ames "atson and #aurice "ilkinsgained acclaim for their elucidation of the
structure of $%& the %obel 'ri(e for #edicineand)or 'hysiology has been won on 2* occasions
by scientists working in human and moleculargenetics or related fields.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
1962
,For their disco-eries concerning the molecularstructure of nucleic acids and its significance forinformation transfer in li-ing material.
Francis /arry Com+ton Crick !ames $ewey "atson #aurice /ugh Frederick "ilkins
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
1962
WatsonCrickdouble helix modelfor the structure of $%&.
0ray diffraction +attern of $%& studied by
Wilkins the s+ots forming a cross in the centerdenote a helical structure. The hea-y bands atthe left and right arise from the recurring bases.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
196
Fran3ois !acob &ndr4 5woff !acues #onod
,For their disco-eries concerning genetic control
of en(yme and -irus synthesis.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
196
Lac operonstudied by Jacob, Monod & Lwoff.&7 8n the absence of lactose the lac re+ressor binds $%& and re+resses transcri+tionfrom the lac o+eron.
7 &llolactose or another inducer binds to the lac re+ressor leading to its dissociationfrom $%& and to the +roduction of lac m:%&.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
1966
'eyton :ous
,For his disco-ery of tumourinducing -iruses.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
1966
Rousshowed that -iruses could +roduce tumors in animals. The first -irus he disco-eredthat +roduced tumors is now called Rous sarcoma virus ;which causes sarcomas in chickens7.
:ous concei-ed for the first time that the change of normal cells to cancer cells was notsudden but occurred through se-eral ste+wise changes. 8n the beginning of this +rocessdesignated by :ous as 'tumour proression' the +otential cancer cells are in a
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
196@
:obert ". /olley /ar Aobind ?horana #arshall ". %irenberg
,For their inter+retation of the genetic code and its
function in +rotein synthesis.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
196@Bach tri+let of bases codes for a singleamino acid.The genetic code is deenerate,unambiuous, non%overlappin, wit!outpunctuation, and universal.
:ough endo+lasmic reticulum wheretranslation of the genetic code in m:%&into +roteins takes +lace.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19D
$a-id altimore :enato $ulbecco /oward #artin Temin
,For their disco-eries concerning the interaction
between tumour -iruses and the genetic materialof the cell.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19D
The existence of en(ymes called reverse transcriptases;that can transcribe -iral :%&into $%& which can integrate into host genome7 in R- retroviruses;such as "$ thehuman immunodeficiency -irus7 was +redicted by "oward *eminin 1962 and theen(ymes were ultimately detected by Temin and inde+endently by /avid #altimorein19D*. Their disco-ery aroused much attention as dogmashaking +roof that geneticinformation can flow ,backward from :%& to $%&.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19D@
"erner &rber $aniel %athans /amilton E. Smith
,For the disco-ery of restriction en(ymes and their
a++lication to +roblems of molecular genetics.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19D@
Restriction endonucleases ;also called restrictionen(ymes7 recogni(e and clea-e $%& at s+ecific $%&seuences ;recognition seuences or restrictionsites7 to generate a set of smaller fragments.
The diagram shows how restriction endonucleases
can be used to clone $%&.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19@*
aru enacerraf !ean $ausset Aeorge $. Snell
,For their disco-eries concerning genetically
determined structures on the cell surface thatregulate immunological reactions.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19@*
8n humans the genetically determined cell surface antigens that regulate immunologicreactions are called !istocompatibilit+ antiens because they were found to be the basisfor reection of foreign trans+lanted tissue.
The most im+ortant of these is the ma0or !istocompatibilit+ comple1 2M"C3of geneslocated on chromosome 6. There are G classes of #/C molecules of which class l
molecules are found on the surface of all nucleated cells and class llmolecules only oncertain cells of the immune system.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19@*
. The human maor histocom+atibility com+lex 2M"C3of genes on chromosome 6 which form #/C class 8 ;region & > C7 88 ;region $7 > 888 molecules.#. Class 8 ;left7 > class 88 ;right7 #/C molecules.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19@G
arbara #cClintock
,For her disco-ery of mobile genetic elements.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19@G
#obile genetic elements also known as
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19@
#ichael S. rown !ose+h 5. Aoldstein
,For their disco-eries concerning the regulation of
cholesterol metabolism.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19@
&s a result of the elucidation of the +athways of cholesterol metabolism se-eral grou+s ofli+idlowering drugs were later de-elo+ed including statins, fibrates, & bile acid bindinresins.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19@D
Susumu Tonegawa
,For his disco-ery of the genetic +rinci+le for
generation of antibody di-ersity.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19@D<hough humans ha-e only aboutG**** genes we can +roduce billionsof different antibodies so eachdifferent antibody cannot be +roducedby a single gene.
&ntibodies are +roduced byrearrangement > somaticrecombinationof +ortions of $, / & Jreionsof genes coding for the twohea-y > one light chain of eachantibody molecule
The inter-ening regions of the genes
between these segments are remo-ed.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19@9
!. #ichael isho+ /arold B. Harmus
,For their disco-ery of the cellular origin of
retro-iral oncogenes.
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
19@9isho+ > Harmus identified the
s+ecifiic gene in the :ous sarcoma-irus that causes neo+lastictransformation > found that similargenes were +resent in normal cells.
Cellular genes that cause cancer;oncoenes7 are designated cEnc todistinguish them from -iral oncogenes-Enc.
% b l i i # di i )'h i l
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
199G
:ichard !. :oberts 'hilli+ &. Shar+
,For their disco-eries of s+lit genes.
% b l i i # di i )'h i l
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
199G
:oberts and Shar+ in 19DD inde+endently of each other obser-ed that a gene in higher
organisms could be +resent in the genetic material as se-eral distinct and se+arate segments;e1ons & introns7 resembling a mosaic.
:oberts and Shar+ also +redicted that a s+ecific genetic mechanism is reuired to enable s+litgenes to direct the synthesis of +roteins.They +ro+osed that messener R-in higherorganisms has to be edited > called the +rocess splicin where the introns are remo-ed >exons linked together.
% b l i i # di i )'h i l
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
199
Bdward . 5ewis Christiane %IssleinHolhard Bric F. "ieschaus
,For their disco-eries concerning the genetic
control of early embryonic de-elo+ment.
% b l i i # di i )'h i l
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
199The antero+osterior > dorso-entral body
axes of the embryo are established due toconcentration gradients of +roducts of-arious genes ex+ressed in a seuentialmanner.
%IssleinHolhard > "ieschaus studied thebicoid > nanos +roteins in the embryo of the
fruitfly Drosophila melanogaster.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
199D
Stanley . 'rusiner
,For his disco-ery of 'rions a new biological
+rinci+le of infection.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
199Drionsare infectious +rotein +articles ;without any nucleic acid7 which cause misfolding ofhost cellular +roteins. They are the cause of a grou+ of ra+idly +rogressi-e fatalneurodegenerati-e diseases in humans and other mammals known as sponiformencep!alopat!ies ;because the brain becomes s+ongyand full of holes7
/uman +rion diseases include Creut4feldt%Jakob disease 2CJ/3, variant Creut4feldt%Jakobdisease 2vCJ/3, 5erstmann%)traussler%)c!einker s+ndrome, fatal familial insomnia,& kuru.
Stained section of a human brain withs+ongiform change.
The globular domain of human +rion +rotein;'r'7.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
1999
AInter lobel
,For the disco-ery that +roteins ha-e intrinsic
signals that go-ern their trans+ort and locali(ationin the cell.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
1999
#lobel's model of +rotein targeting to s+ecific cellular com+artments. ;S:'= signalrecognition +article7. %ewly synthesi(ed +roteins ;on ribosomes7 ha-e a signal seuence
That guides them to the a++ro+riate subcellular com+artment.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
2***
&r-id Carlsson 'aul Areengard Bric :. ?andel
,For their disco-eries concerning signal
transduction in the ner-ous system.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
2***Carlsson+ro-ed that dopamineis a
neurotransmitter. /e then usedreser+ine on animals to de+letedo+amine from +resyna+tic terminalsand found that the animals lost theirability to mo-e. /e showed that theanimals regained their ability to mo-ewhen he ga-e them 5$E'&.
5reenardshowed what ha++enswhen do+amine and other similartransmitters stimulate a neuron. /edisco-ered the mechanism of sinaltransductionin the ner-ous systemby +rotein kinases when
neurotransmitters bind to rece+tors onthe +ostsyna+tic membrane.
(andel showed that formation ofmemoriesin the brain is a function ofneuronal syna+ses. /e elucidated themechanism of formation of memories.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
2**1
5eland /. /artwell Tim /unt Sir 'aul #. %urse
,For their disco-eries of key regulators of the cell
cycle.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
2**1
'hases of the cell cycle= A1 S A2 # > A*.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
2**1
Cell c+cle reulators= cyclins > cyclinde+endent kinases cause +rogression throughdifferent +hases of the cell cycle.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
2**2
Sydney renner /. :obert /or-it( !ohn B. Sulston
,For their disco-eries concerning genetic
regulation of organ de-elo+ment and+rogrammed cell death.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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%obel +ri(e in #edicine)'hysiology
2**2
Ste+s in prorammed cell deat!> the genes in-ol-ed.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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+ y gy
2**6
&ndrew J. Fire Craig C. #ello
,For their disco-ery of :%& interference gene
silencing by doublestranded :%&.
%obel +ri(e in #edicine)'hysiology
8/9/2019 Nobel Laureates in Genetics
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+ y gy
2**6R- interference 2R-i3.
Bxogenous doublestranded :%&s;dsR-7 or endogenous short hair+in:%&s ;s!R-7 are clea-ed by theen(yme dicer into small interfering :%&s;siR-7 which are unwound by ahelicase into single strands.
Ene ;antisense7 strand of si:%& binds to> acti-ates R)C;R%&induced silencingcom+lex7.
:8SCs bind to > clea-e m:%&s in aseuences+ecific manner thus silencings+ecific genes by +re-enting theirtranslation.
R-i has broad thera+eutic a++licationsfrom treatment of cancers to -iralinfections such as /8H > neurodegenerati-e disorders like /untington
8/9/2019 Nobel Laureates in Genetics
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+ y gy
2**D
#ario :. Ca+ecchi Sir #artin !. B-ans Eli-er Smithies
,For their disco-eries of +rinci+les for introducing
s+ecific gene modifications in mice by the use ofembryonic stem cells.
8/9/2019 Nobel Laureates in Genetics
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Workshop On Recent Advances In GeneticsWorkshop On Recent Advances In Genetics
GENETICS 2009GENETICS 2009
1919thth
Fer!ar" 2009Fer!ar" 2009
#$ %$ &ati' (niversit"#$ %$ &ati' (niversit")o'hap!r)o'hap!r