TRNG I HC KHOA HC T NHIN TR H H T I HC THI NGUYN TH H ---------------

MN HC: CNG NGH HO SINH

PGS.TS. L Thanh Ha Vin Cng ngh sinh hc Vi ngh Vin Khoa hc v Cng ngh Vit Nam Vi ngh Vi18. Hong Quc Vit, Cu Giy, H Ni; Ho Qu Vi Gi T: 04-37567297; 0912336855; Email: imibtvn@gmail.com T: 04-

CNHS+SHPT

Bi ging u Phn I: Cng ngh gen nn tng ca cng ngh ha sinh Bi ging 1 c im cu trc genome v gene ca procaryote v eukaryote 1.1. c im cu trc h gen (genome) v gen ca procaryote 1.2. c im cu trc h gen (genome) v gen ca eucaryote Bi ging 2 Cc yu t cn thit trong cng ngh gen 2.1. Chun b gen cn tch dng 2.2. Cc loi enzyme thng s dng trong cng ngh gen 2.3. Vector tch dng v vector biu hin 2.4. Cc h thng biu hin Bi ging 3 Nguyn l ca cng ngh gen 3.1. Cc bc tin hnh ch yu ca cng ngh gen 3.2. Nguyn tc chn vector tch dng v biu hin 3.3. K thut bin np vector ti t hp vo t bo ch 3.4. K thut chn lc dng t bo ti t hp Phn II: Vaccine v qu trnh sn xut vaccine Bi ging 4 Khi nim vaccine v tnh min dich 4.1. Khi nim vaccine v tnh min dich 4.2. Phn loi vaccine Bi ging 5 Quy trnh cng ngh sn xut vaccine 5.1. Quy trnh cng ngh sn xut vaccine c truyn 5.2. Quy trnh cng ngh sn xut vaccine th h mi Phn III: Cng ngh ln men sn xut khng sinh Bi ging 6 i cng v cht khng sinh 6.1. Khi nim cht khng sinh 6.2. Cc bc c bn to cht khng sinh dng trong y hc Bi ging 7 Cng ngh sn xut khng sinh penicillin 7.1. C s l thuyt 7.2. Quy trnh sn xut khng sinh penicillin trong cng nghip Bi ging 8 Cng ngh sn xut khng sinh cephalosporin 8.1. C s l thuyt 8.2. Quy trnh sn xut khng sinh cephalosporin trong cng nghip Bi ging 9 Sn xut khng sinh bn tng hp 9.1. Sn xut 6 APA 9.2. Sn xut khng sinh bn tng hp t 6 APA

Thi gian

*Acid nucleic *Plasmid *Enzyme hn ch *Vector *Nguyn l CN gen

*Vaccine v Min dch *SX vaccine

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Ho sinh (biochemistry) v cng ngh ho sinhTrong thi i hin nay, nghin cu ho sinh khng ch dng li mc th hi ho ch l thuyt, tm hiu cu trc chc nng v mi lin quan sinh hc, m cn thuy hi tr ch thit phi ni n vic nghin cu i su vo chiu su ca cu trc chc tr ch thi ph vi chi nng t bo mc DNA (phn t) v tn dng DNA to nn sn phm ph phc v i sng, hay ni cch khc l lnh vc nghin cu sinh hc ph ng, kh phn t gen v h gen (Molecular biology of the genes and genomes). Nghin cu ho sinh (biochemistry) l mt phn ch yu nht trong cc lnh ho ph ch nh vc lin quan n sinh hc phn t (molecular biology) ca t bo. Bt k mt lnh vc no trong nghin cu sinh hc, d phm vi nh hay phm vi ph nh ph ln, xu hng ca tin trnh nghin cu v ng dng cng c sp t h ti tr tun t t vic nghin cu c bn (basic research) n p dng trin khai tri tu vi th nghim (development) v n giai on tn dng cng ngh sn xut th nghi o ngh xu sn phm (biotechnology and/or bioindustry). ph bioindustry).

N/C C BN >>> CNG NGH >>> CNG NGHIP B NGH

Ho sinh (biochemistry) v cng ngh ho sinh (biochemical technology) Ho ngh ho bao gm c ho sinh phn t (molecular biochemistry) v cng ngh ho ngh ho sinh phn t (molecular biochemical technology/industry), l ho lnh vc nghin cu rt rng v chc nng c th sng v qui lut c ch th lu bn trong nghin cu ng dng ho sinh v ho sinh phn t. ho ho Ho sinh phn t, thc cht l sinh hc phn t t bo nghin cu cu Ho th ch trc chc nng hot ng ca t bo mc phn t; v cng ngh tr ch ho ngh ho sinh phn t l s trin khai kt qu nghin cu ho sinh phn t tri qu ho ho gc cng ngh m nn tng ch yu l cng ngh gen (genetic ngh ch ngh engineering) hay cn gi l cng ngh sinh hc phn t (molecular ngh biotechnology). Cng ngh ho sinh phn t (cng ngh gen, cng ngh sinh hc phn ngh ho ngh gen, ngh t) l lnh vc tha hng nhng kt qu nghin cu c bn v DNA, th h nh qu gen, h gen, protein v mi tng tc mc phn t trong t bo gen, gen, v c th; v l lnh vc khng th tch ri t bo hc (cytology), th th sinh hc phn t t bo (molecular cell biology), di truyn hc t bo truy (cytogenetics), cng ngh ti t hp (DNA and protein recombinant cytogenetics), ngh technology) v mt lnh vc thit yu mi pht sinh, l tin-sinh hc thi ph sinh, tinv cng ngh tin-sinh hc (bioinformatics and information technology). ngh tin-

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Cng ngh gen v cng ngh sinh hc phn t, trong giai on hin ngh ngh o hi ti (th k 21), cn bao gm c cng ngh nano sinh hc phn t; v th ngh do nhu cu thc t pht sinh cng nh iu kin cho php, c th th ph i ki ph th t nhng bc u tin ca nn cng nghip hin i, cng nghip nghi hi nh b nghi sinh hc v gen v sinh hc phn t (genetic engineering technology; molecular bioindustry). bioindustry). Cng ngh ha sinh gn lin vi cng ngh sinh hc phn t (ni ngh li ngh gn l cng ngh gen), do vy, tm hiu nguyn l v phng thc gen), th ngh hi ng dng SHPT l ht sc cn thit. thi Trong qu trnh thc hin cng ngh gen, nhng vn mu cht qu tr th hi ngh gen, nh ch cn nm chc l: ch Cu trc v nguyn l hot ng ca acid nucleic (ADN, ARN). ho ARN tr H thng plasmid v cu trc vector trong CNSH. th tr H thng t bo ch ca plasmid v vector (E. coli). th ch (E. coli). PCR; RT-PCR; thao tc sn phm, tch dng chn lc ti t hp. RT ph ch Tin-sinh hc ng dng trong x l chui gen. chu TinTi liu cn trch dn: L Thanh Ha (2002). Sinh hc phn t: nguyn l v ng dng. Vin Cng ngh sinh hc. Ti liu ging dy sau i hc. V Th Thng Lan (2007). Gio trnh sinh hc phn t t bo v ng dng. Nh xut bn Gio dc.

Sinh hc phn t: nn tng v tm quan trng trong cng ngh gen v tr ngh hng nghin cu ng dng chn on phn loi ph h tin ho, di lo ph ho h ch o truyn qun th, bnh l phn t v sn xut ch phm ti t hp truy qu th xu ch phSinh hc phn t (molecular biology) l mt lnh vc quan trng khm ph ph h gen bn trong, nghin cu cu trc, mi tng quan v biu hin kiu gen (genotype) ca i tng. Nh vy, ni n sinh hc phn t ngha l ni n cc loi kin thc c bn v gen v di truyn cng nh cc loi k thut nhm phc v cho qu trnh nghin cu v thc nghim lnh vc ny. Chng ta cng cn phn bit chnh xc cc phn ngnh c bn ca sinh hc phn t: nghin cu chn on (molecular diagnosis) v gim nh (molecullar gi ch Identification); nghin cu phn loi (molecular classification) v quan h loi ph lo lo (molecular taxonomy); nghin cu ph h (molecular phylogeny), tin ho ph ho lch s (molecular evolutionary history), di truyn phn t (molecular genetics) v nhiu lnh vc khc. Cc phn ngnh c bn ny ca sinh hc phn t khng ng ring l, m thnh qu ca mi mt loi hnh nghin cu c tc dng tng tc h tr cho cc ng tr phn ngnh lin quan tn dng d liu tin trnh nghin cu v ng dng thun li hn, chnh xc hn.

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Trong thi i hin nay, ni n nghin cu sinh hc phn t, phi cn thit ni n vic s dng v tn dng cc loi k thut v cng c hin i, trc lo thu hi i ht phi k n cc k thut ADN v protein (DNA and protein technology), v cc cng c v dng c, trang thit b, bao gm cc chng trnh tin-sinh hc c, b (bioinformatics) v cc loi thit b k thut cao nh my nhn bn ADN (my PCR; real-time PCR), my tnh (computer), my giI trnh t v nhiu h thng h tr khc. V nguyn tc: nguy Trong cng mt ging (genus) mi tng quan phn t c khai thc kha cnh tm hiu lin quan phn loi. Khi mi quan h ca loi v loi c li ph lo nghin cu xa hn, h thng hn, th mi quan h khng dng mc phn loi na m tin xa hn v lin quan ph h v lch s tin ho. li ph ho Nghin cu h thng ph h, to nn cy ph h (phylogenetic tree) phi da ph vo k thut sinh hc phn t gp phn chnh xc ha h thng phn loi ni chung v gp phn cung cp d liu cho vic thit lp qu gen bo tn qu chng. S kt hp v ng dng cng ngh sinh hc phn t trong nghin cu sinh thi to nn mt mi quan h mt thit ca mt loi hnh nghin cu mi: cng ngh sinh thi hc phn t (molecular eco-biotechnology). ngh th ph

Phn bit tnh thun chng v t hp lai ca cc loi, trong c cc loi ng thu ch vt m s lng tn ti cn rt t, hoc tnh nng sinh sn bo v loi rt chm, nu hon ton da vo c tnh ngoi hnh (phn loi hnh thi) s khng m ngo bo c s vng vng v di truyn hc, c nguy c s dn n nhng nguy hi trong nhng th h tip theo. Khi sinh hc phn t thc s c ng dng rng ri, Ngn hng Gen v cc Trung tm D liu quc t (Data Base) lu tr s liu i din cho nhiu chng loi quan h gn, v iu kin nghin cu v ng dng cho php, th vic nghin cu phn loi, ph h l s kt hp ca nghin cu phn loi hnh thi da trn kiu hnh, vi nghin cu phn loi sinh hc phn t da trn kiu gen. Trong h gen cha nhim sc th (h gen ca nhn t bo), khng phi tt c cc vng gen u n nh (DNA stability), m h gen c phn chia thnh nhng vng c tnh n nh cao, n nh thp v bt n nh. nh cao Nhng vng bt n nh (unstable) thng thng cha rt nhiu nucleotit thuc hnh Anin (A) v Thymin (T), hay ngc li, Guanin v Cytosin; ni cch khc hm lng A+T rt cao hoc ngc li.

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Vng bt n nh cng thng li l vng c nhiu cu trc lp 2, 3, hoc 4 tr ho nucleotit (tandem repeats), hoc hng chc nucleotit (mini-satellite) v chng l i tng ca s gin n ca gen hoc trt t nucleotit trong vng, dn n hu qu di truyn rt nng n. Nhng gen nm trong cc vng n nh cao v thp c chia lm hai nhm: nhm gen gi nh (house-keeping genes) v nhm gen i ph (contingency gi nh genes), trong nhm gen gi nh c h s t bin thp, sn phm ca chng c tnh bo tn chc nng nghim ngt, cn nhm gen i ph c h s t bin cao, to sn phm linh hot trong c ch thch ng i ph vi s thay i ca mi trng. Hu nh tt c cc gen i ph ny khng hoc t c coi l i tng nghin cu ca sinh hc phn t trong xy dng ph h v phn loi. Phng php sinh hc phn t ang c ng dng ngy cng rng ri v c ph hiu qu trong mi lnh vc sinh hc. l vic s dng cc k thut ADN (trc thu ht l k thut PCR) v k thut protein xc nh chui gen hay chui acid thu thu PCR amin ca tng gen, cng nh lp bn gen ca tng khu vc nht nh trong h gen ca loi cn chn on so snh i chiu vi nhng loi khc, nhm xc nh chnh xc loi mong mun. i vi nghin cu bnh l phn t, chng ta cn hiu rng, trong cc t hp gen ca mt i tng, c mt (s) gen chu trch nhim m ho cho protein chc nng, do vy t bin trong gen s lm thiu nng ho chc nng ca chng. Xc

nh c gen bnh ngha l chng ta chn on c nguyn nhn gy ngh ch ch nguy nh bnh v tm hiu bnh l phn t ca chng. Bnh l phn t cn lin quan n ph ch ng. ph li hi sai lch cu trc gen v thiu nng hot ng do di truyn to nn bnh l. tr thi ho l. Trong trng hp ny, chng ta c th gi hin tng ny l bnh l di truyn tr ch th hi ng phn t. ph i vi nghin cu tc nhn gy bnh, chng ta cng cn hiu rng vi sinh vt (vi khun, c bit l virus) c h gen n gin (prokaryote), xc nh gen quyt nh tnh c lc (gen gy bnh) c ngha quan trng trong nghin cu sinh bnh hc, tin ho phn t, quan h VSV-c th v pht trin vaccine v ch phm chn on. Trong cng ngh gen hin i to vaccine th h mi, ct b gen c hoc bin i n, s to nn c chng nhc c lm vaccine. Nhng chng nh th ny c gi l vaccine nhc c cng ngh gen. i vi nghin cu pht trin vaccine, chng ta cn hiu rng, trong v s cc gen ca VSV c mt (s) gen quyt nh protein mang tnh khng nguyn thng l protein cu trc b mt, do vy, nghin cu gen khng nguyn cho bit tnh khng nguyn mnh hay yu, phn lp gen gn vo vector biu hin s cho ch phm vaccine di nhm (polypeptide), hoc ch phm chn on, hoc vaccine ADN v nhiu hng ng dng khc. Nh vy sinh hc phn t ngy nay l mt lnh vc a ngnh c vai tr tin ng ng quyt trong xc nh, phn lp, thao tc v ng dng gen v h gen. nh, quy

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