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BAB 12 REKAYASA GENETIKA DAN MOLEKUL KEHIDUPAN 1 Pokok Bahasan The Chemistry of Heredity The Double Helix of DNA Cracking the Chemical Code Protein Structure and Activity: Form and Function The Human Genome Project Genetically Engineered Medical Treatments Genetically Engineered Agriculture Cloning Mammals and Humans The New Prometheus? 2 The Chemistry of Heredity (Kimia Keturunan) Konsep Dasar Genetik Human Genome: - 10 million million (10x1012) cells with a nucleus - each cell has a complete set of genetic instructions to make another you(biologically) - 23 pairs of chromosomes - 100,000 genes - def’n: totality of human hereditary information in molecular form 4 Konsep Dasar Genetik Human genome adalah sekumpulan informasi genetik pada manusia Yang terdiri atas : Berjuta-juta cell dengan intinya ( 10 x 1012 ) Tiap-tiap cell memiliki sekumpulan perintah genetik untuk membuat cell yang baru (membuat keturunan baru) 23 pasangan khromosom 100.000 gene [ rangkaian DNA (deoxyribonucleic acid)] Informasi lengkap keturunan manusia dalam bentuk molekular Genome, the total genetic information possesed by an organism Human genome adalah informasi genetik pada manusia DNA DNA (deoxyribonucleic acid): molecule that carries genetic information in all species - DNA of one cell unraveled = 2 meters long 3 parts to DNA: (i) Phosphate group (ii) Sugar (deoxyribose) (iii) Nitrogen bases 7 DNA Put all 3 groups together, called a nucleotide Adenosine phosphate A DNA molecule consists of thousands of nucleotides put together in a long chain (left) 8 The percenst base composition of DNA for various species Species Common Name Adenine Thymine Guanine Cytosine Homo sapiens Human 31.0 31.5 19.1 18.4 Drosophila melanogaster Fruit fly 27.3 27.6 22.5 22.5 Zea mays Corn 25.6 25.3 24.5 24.6 Neuspora crassa Mold 23.0 23.3 27.1 26.6 Escherichia coli Bacterium 24.6 24.3 25.5 25.6 Bacillus subtillis Bacterium 28.4 29.0 21.0 21.6 9 The Double Helix of DNA X-Ray Diffraction of DNA • R. Franklin • J. Watson & F. Crick • 1962 Nobel in Chemsitry 11 DNA Turns out that: Adenine bonds with Thymine Guanine binds with Cytosine Called complementary bases: A=T G=C 12 DNA Double Helix DNA is double stranded and is shaped like a spiral staircase. Ex. What is the complementary strand of DNA for the following sequence: ATAGCCG 13 DNA Replication 14 Cracking the Chemical Code DNA: Blueprint of Life? How does DNA provide genetic information, where does the information come from? 16 DNA: Blueprint of Life? How does DNA provide genetic information, where does the information come from? Key is in the sequences of nitrogen bases. DNA: blueprint for making proteins Proteins: made up of amino acids consist of/or regulate everything in the chemistry of life 17 DNA to Proteins OK, the instructions are in the sequence of bases. There are 20 amino acids How many bases encode for an amino acid? 18 DNA to Proteins OK, the instructions are in the sequence of bases. There are 20 amino acids How many bases encode for an amino acid? if it were 1 base = 1 amino acid, then there would only be 4 amino acids found in proteins. There are up to 20 amino acids found in proteins. 19 DNA to Proteins OK, the instructions are in the sequence of bases. There are 20 amino acids How many bases encode for an amino acid? if it were 1 base = 1 amino acid, then there would only be 4 amino acids found in proteins. There are up to 20 amino acids found in proteins. if it were 2: 42 = 16, not enough 20 DNA to Proteins OK, the instructions are in the sequence of bases. There are 20 amino acids How many bases encode for an amino acid? if it were 1 base = 1 amino acid, then there would only be 4 amino acids found in proteins. There are up to 20 amino acids found in proteins. if it were 2: 42 = 16, not enough 3 bases: 43 = 64 3 bases = codon 21 Codon table 22 DNA to Proteins Transcription: DNA to mRNA Translation: mRNA to protein 23 Protein Structure and Activity: Form and Function Polypeptide Backbone 25 Protein structure • The peptide bond allows for rotation around it and therefore the protein can fold and orient the R groups in favorable positions • Weak non-covalent interactions will hold the protein in its functional shape – these are weak and will take many to hold the shape 26 Secondary structures • 2 regular folding patterns have been identified – formed between the bonds of the peptide backbone • -helix – protein turns like a spiral – fibrous proteins (hair, nails, horns) • -sheet – protein folds back on itself as in a ribbon –globular protein 27 Tertiary structure • The overall fold result in increase in stability • The shape is maintained through H-bond, intermolecular ionic and covalent bond and interactions of amino acid residues with water 28 Protein function – – – – Enzymes, exp : chymotrypsin Structural, exp: collagen, hair Transport : hemoglobin etc – Sickle cell anemia differs from normal blood cell due to replacement of hemoglobin amino acid two glutamic acid by valine – Hemoglobin is a transport protein 29 The Human Genome Project What is the Human Genome Project? • International effort to map all gene in human organism • Started in 1989 lead by J. Watson • Finished June 26, 2000 (co-announced by President Bill Clinton and PM Tony Blair) Definition: GENOME – the whole hereditary information of an organism that is encoded in the DNA. • Aims of the project: – – to identify the approximate 100,000 genes in the human DNA. determine the sequences of the 3 billion bases that make up human DNA. – store this information in databases. develop tools for data analysis. address the ethical, legal, and social issues that arise from genome research. – – 31 Whose genome is being sequenced? - the first reference genome is a composite genome from several different people. generated from 10-20 primary samples taken from numerous anonymous donors across racial and ethnic groups. 32 Benefits of Human Genome Project research • improvements in medicine. • microbial genome research for fuel and environmental cleanup. • DNA forensics. • improved agriculture and livestock. • better understanding of evolution and human migration. • more accurate risk assessment. 33 Genetically Engineered Medical Treatment Recombinant DNA: manipulating gene pools Cut out DNA that encodes for human insulin Splice it into E. Coli plasmid (DNA) Ecoli reads DNA and starts making insulin. Human Growth Hormone (HGH): previously, a 1 year supply required harvesting the pituitary glands from 80 human cadavers • DNA recombinant technology offers many biocatalysis • Greener reaction condition • Atorsvastatin produced from (R)-4-cyano-3hydroxybutyrate which was produced by process using biocatalyst (enzyme) • The enzyme was a product of DNA recombinant 37 Genetically Engineered Agriculture Transgenic plants (organisms) • Artificially created higher plants and animals that share the genes of another species • The focus of development – Improve production stability – Give nutritional benefits to the consumer – Reduce environmental effect of intensive and extensive agriculture – Increase the availability of pharmaceutical and vaccines 39 How to create transgenic plants Agrobacterium tumefaciens DNA containing gene for desired trait Ti plasmid T DNA Restriction site Insertion of gene into plasmid using restriction enzyme and DNA ligase Recombinant Ti plasmid Plant cell Introduction Regeneration into plant of plant cells in culture T DNA carrying new Plant with new trait gene within plant chromosome • Nitrogen fixing corn, corn that capable in fixing N2 • Contain nitrogen fixing bacterial genes • Transgenic soybeans which is resistance to herbicides 41 Mixing Genes: Transgenic Organisms Cloning Mammals and Humans Do you know these movies? Jurassic Park The Lost World The Boys from Brazil Sleeper. Multiplicity Invasion of the Body Snatchers Stepford Wives A Stolen Life Clones The Clones of Bruce Lee Blade Runner Star Wars. Judge Dredd American Ninja 2 Twins Gattaca Alien Resurrection 44 Nuclear transfer/ Somatic cell nuclear transfer (A, B) nucleus is sucked of cell (C) New nucleus is picked up (D) Nucleus/DNA is inserted into the egg 45 Dolly, 1996-2003 46 Snuppy, 2005 Snuppy and his “father” Snuppy and his surrogate mother 47 Human cloning • Many reports said the success of the somatic nuclear transfer • After electrical jolt, the embryo started growing • No report of embryo development to human • The intention of researcher is to harvest stem cell 48 The New Prometheus? • We have found key natural compounds of life “DNA” • We have clone gene and took many advantage for human being • We have clone animals • Next logical step would be creating new organism or cloning human “the super one” • However we could not removed defective gene from the pools • And cloning or creating superman could end up with creating a new promatheus 50 Thank you 51