Introduction to Biological Engineering 1. Introduction to Biological Engineering and Bioprocesses Biological Engineering/Biotechnology Landmarks and Technologies Miguel Prazeres Biotechnology Technology based on biology the use of cellular and biomolecular processes to solve problems or make useful products Miguel Prazeres Milestones vaccines fermentation 4000-8000 BC 1st genome sequence H. influenza penicillin DNA recombinant structure DNA microbiology 1797 monoclonal antibodies 1857 1928 1953 PCR Dolly human genome 1973 1975 1983 ‘95 ‘97 2000 Traditional Biotechnology New Biotechnology food and beverage, primary & secondary metabolite, waste treatment… biopharmaceuticals, antibodies, tissues, stem cells, enzymes… Miguel Prazeres The birth of modern Biotech “Process for producing biologically functional molecular chimeras” U.S. Patent No. 4,237,224 1972 Stanley Cohen and Herbert Boyer combined their efforts to create recombinant DNA technology Miguel Prazeres Recombinant DNA Technology DNA protein Miguel Prazeres US 4,237,224 Date Title Inventors Assignee Submission date http://www.google.com/patents Miguel Prazeres Revenues Cohen-Boyer US$ 255 000 000 10% annual fees 90% royalties 2442 products, 468 companies, US$35 billion sales during patent life Biotechnology landmarks 1953 – James Watson and Francis Crick publish structure DNA 1958 – Mather Meselson and Franklin Stahl demonstrate how DNA replicates 1961-63 – researchers crack the genetic code linking gene to protein 1972 – Paul Berg and colleagues create 1st rDNA molecules using restriction enzymes 1973 – Cohen and Boyer describe rDNA techniques 1975 – Köhler and Milstein describe cell line able to produce monoclonal antibodies 1980 – US Supreme Court decides Diamond vs Chakrabarty 1982 – first rDNA-based drug marketed: Humulin (human insulin) 1984 – first genetically engineered vaccine developed (hepatitis B) 1986 – a-interpheron approved for cancer; first monoclonal antibody approved; Leroy Hood and Lloyd Smith automate sequencing; kick off of human genome project Miguel Prazeres Biotechnology landmarks 1987 – Chiron sells 1st genetically engineered vaccine; human growth hormone developed 1988 – 1st US patent issued for transgenic mice; genome project funded by US congress 1989 – Epogen approved for renal disease anemia 1990 – first human gene therapy for immune disorder 1991 – Craig Venter invents EST technology 1995 – first genome sequence of free living organism published: Haemophilus influenza 1997 - Dolly the sheep born- first clone of adult mammal 1998 – Celera genomics proposes to sequence human genome first 1999 – first human chromosome sequence published 2000 – race to sequence human genome declared tie between Celera Genomics and Human genome project 2010- synthesis of a bacterial genome from a computer record Miguel Prazeres Technologies and Tools Recombinant DNA technology Hybridomas and monoclonal antibodies Bioinformatics, genomics, proteomics, metabolomics… Cloning, sequencing ,PCR, oligonucleotide and gene synthesis….. Protein, metabolic, cell and tissue engineering Bioprocessing technology Biosensors, microarrays Highthroughput screening, drug discovery, gene and protein synthesis… Nanobiotechnology, biomicrofluidics Synthetic biology…. Miguel Prazeres Hybridomas and Monoclonal Antibodies monoclonal antibody Miguel Prazeres Hybridomas and Monoclonal Antibodies monoclonal antibody (~150 000 g/mol) Miguel Prazeres Bioinformatics Sequence analysis, structure visualization, structural analysis, molecular simulation and dynamics, molecular docking, chemoinformatics, data mining… Miguel Prazeres Oligonucleotide Synthesis (~ 0.25 € /nt) oligo1 A C A G C G T A T G T A oligo 2 A C C GGG T oligo 3 T G T A (e.g. https://eu.idtdna.com/) Miguel Prazeres PCR: Polymerase Chain Reaction Miguel Prazeres Gene Synthesis target gene sequence (ATTCGCGGGT….) oligo pool PCR steps final gene Miguel Prazeres Metabolic Engineering Miguel Prazeres Bioprocessing Miguel Prazeres Microarrays Miguel Prazeres Highthroughput … screening, drug discovery, gene synthesis , protein expression... 6, 24, 96, 384 or 1536 sample wells Miguel Prazeres Microfluidics Miguel Prazeres Nanobiotechnology Miguel Prazeres Synthetic Biology Miguel Prazeres Webography PubMed: a free search engine accessing databases of references and abstracts on life sciences and biomedical topics https://www.ncbi.nlm.nih.gov/pubmed Protein Databank: 3D shapes of proteins, nucleic acids, and complex assemblies http://www.rcsb.org/pdb/home/home.do ExpPASy: Bioinformatics Resource Portal which provides access to scientific databases and software tools in different areas of life sciences including proteomics, genomics, phylogeny, systems biology, population genetics, transcriptomics etc. https://www.expasy.org/ Pymol an open source molecular visualization system you can download to your pc https://www.pymol.org/ IDTA: a company providing custom oligonucelotides synthesis https://eu.idtdna.com/pages/products/dna-rna/custom-dna-oligos Miguel Prazeres
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