Molecular Biology 2015 winter term -Jung-Hye Choi Rm #226/205(Mol. Biol. Lab) jchoi@khu.ac.kr Lecture Textbook: Lehninger principle of biochemistry Lippincott’s illustrated Reviews Biochemistry Evaluation: final-term 60% + attendance 10% + participation 30%

Molecular Biology From wikipedia Molecular biology /məˈlɛkjʊlər/ is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry. Molecular biology chiefly concerns itself with understanding the interactions between the various systems of a cell, including the interactions between the different types of DNA, RNA and protein biosynthesis as well as learning how these interactions are regulated.

Biochemistry is the study of the chemical substances and vital processes occurring in living organisms. Biochemists focus heavily on the role, function, and structure of biomolecules. The study of the chemistry behind biological processes and the synthesis of biologically active molecules are examples of biochemistry. Genetics is the study of the effect of genetic differences on organisms. Often this can be inferred by the absence of a normal component (e.g. one gene). The study of "mutants" – organisms which lack one or more functional components with respect to the so-called "wild type" or normal phenotype. Genetic interactions (epistasis) can often confound simple interpretations of such "knock-out" studies. Molecular biology is the study of molecular underpinnings of the process of replication, transcription and translation of the genetic material. The central dogma of molecular biology where genetic material is transcribed into RNA and then translated into protein, despite being an oversimplified picture of molecular biology, still provides a good starting point for understanding the field Lehninger Principles of Biochemistry 6th Ed

Information pathways - Genes and chromosomes - DNA metabolism - RNA metabolism - Protein metabolism - Regulation of gene expression

Genetics and cell biology are revolutionizing medicine and agriculture. Molecular biology is providing new tools for investigating ancestry and solving crimes. GMO A genetically modified organism (GMO) or genetically engineered organism (GEO) is an organism whose genetic material has been altered using genetic engineering techniques. These techniques, generally known as recombinant DNA technology, use DNA molecules from different sources, which are combined into one molecule to create a new set of genes. This DNA is then transferred into an organism, giving it modified or novel genes. Transgenic organisms, a subset of GMOs, are organisms that have inserted DNA from a different species. GMOs are the constituents of genetically modified foods. (from wikipedia)

FIGURE 9-30 Tomato plants engineered to be resistant to insect larvae FIGURE 9-30 Tomato plants engineered to be resistant to insect larvae. Two tomato plants were exposed to equal numbers of moth larvae. The plant on the left has not been genetically altered. The plant on the right expresses a gene for a protein toxin derived from the bacterium Bacillus thuringiensis. This protein, introduced by a protocol similar to that depicted in Figure 9-28, is toxic to the larvae of some moth species while being harmless to humans and other organisms. Insect resistance has also been genetically engineered in cotton and other plants. FIGURE 9-30 Tomato plants engineered to be resistant to insect larvae. Two tomato plants were exposed to equal numbers of moth larvae. The plant on the left has not been genetically altered. The plant on the right expresses a gene for a protein toxin derived from the bacterium Bacillus thuringiensis. This protein, introduced by a protocol similar to that depicted in Figure 9-28, is toxic to the larvae of some moth species while being harmless to humans and other organisms. Insect resistance has also been genetically engineered in cotton and other plants.

Genetic Testing Rationale -Predictive testing > Am I at risk for a genetic disease? -Diagnostic testing > Does my disease have a genetic basis -Carrier Testing > Might I pass on a genetic mutation to a potential child? Prenatal testing > Does my disease have a genetic basis?

NGS(next generation s cost over time…. -개인 유전체 시대 -메타 유전체 시대 -100만원 유전체 시대 -10만명 유전체 시대 -유전체 소매상 시대: deCODEme, 23andMe, Knome

Proteins and other effectors Personalizing Healthcare Clinical Data Genome Anatomy Genome Physiology Proteins and other effectors Zetabyte Persoanl Using Personal and Private Big data The patient has disease A, subclass B, which will likely respond to drug C

-New Technologies promise to expedite the discovery of New pharmaceuticals >Therapies are arrived at by identifying an enzyme or receptor involved in the process and discovering an inhibitor that interferes with its action. Ex. The vasoconstriction it induces can cause or exacerbate hypertension, congestive heart failure, and coronary artery disease >Proteomics will play an increasing role in identifying such potential drug targets. Ex. Urotensin II and GPR14 interaction demonstrated by protein-protein interactions.=> GPR14, a key target for drug therapies! Lehninger Principles of Biochemistry 6th Ed

Gleevec (imatinib mesylate) “Magic Bullet” “Miracle drug” Discoveries leading to FDA approval of Gleevec(STI571) for treatment of CML Gleevec (imatinib mesylate) “Magic Bullet” “Miracle drug” 1960 1960-Abnormal chromosome 22 observed in CML patients 1970 1973-Chromsome 22 and 9 translocation observed by new staining techniques 1980 1982-abl Proto-oncogene identified in chromosome 22 translocation 1984-1987-BCR-ABL protein identified as possible cause of CML 1990 1990-bcr-abl Gene identified as cause of leukemia in mice 1993-First STI1571/Gleevenc laboratory studies begin 1998-first human testes begin 1999-first human results reported thereby stopping cancer growth. When Gleevec came to market about four years ago, it was widely hailed as a miracle drug. For the first time, there was hope for this group of patients. Chronic myeloid leukemia….Novartis's (NYSE: NVS) Gleevec (imatinib mesylate) was touted as a "magic bullet" for the treatment of chronic myelogenous leukemia (CML). But there is a big difference between magic and medicine. Medicine has limitations. As often occurs with medicines, patients with CML can become resistant to treatment with Gleevec. Approximately 8,000 new cases of CML are diagnosed each year. 2000 2001-April: Larger study confirms earlier findings 2001-May:FDA approves ST1571/Gleevec for treatment for CML

-Recombinant DNA technology yields new products and challenges >The products of recombinant DNA technology range from proteins to engineered organisms. -The technology can produce large amounts of commercially useful proteins, can design microorganisms for special tasks, and can engineer plants or animals with traits that are useful in agriculture or medicine. -Some products of this technology have been approved for consumer or professional use, and many more are in development. Genetic engineering has been transformed over a few years from promising new technology to a multibillion-dollar industry, with much of the growth occurring in the pharmaceutical industry. Some major classes of products are listed in Table 9-4 Ex) Erythropoietin-stimulate erythrocyte production The extraordinary promise of modern biotechnology dose not come without controversy. Lehninger Principles of Biochemistry 6th Ed

생물의약품 [ biomedicine , 生物醫藥品 ] 재조합 DNA 기술을 응용하여 제조한 의약품. 대표적인 예로 펩티드호르몬, 백신, 인터페론, 인슐린, 사람성장호르몬, B형 간염백신, 인터루킨 2, γ형 인터페론, 혈전용해제(TPA) 등이 있음.

전 세계 의약품 판매순위 톱 10에서 2000년에는 1개뿐이던 바이오의약품이 2008년에는 5개로 증가, 2014년에는 10개 중 7개를 차지할 것으로 예상하고 있다. 또한 향후 5년 내에는 총 189조원 규모로 30% 이상 증가할 것으로 보고 향후 블록버스터급 바이오신약의 특허만료가 도래함에 따라 바이오시밀러(Biosimillar) 시장 역시 대폭 성장해 2조원을 넘어설 것으로 예상된다. http://news.khan.co.kr/kh_news/khan_art_view.html?artid=201402262040345&code=920509

http://mbnmoney.mbn.co.kr/news/view?news_no=MM1000844475

5년 후면 생물의약품 시대 온다 매출액 상위 10대 의약품 중 7품목 달해 5년 후면 세계에서 가장 잘 팔리는 10대 의약품 중 생물의약품이 7개 품목에 달해 생물의약품의 시대가 올 것으로 예상된다.   이밸류에이트 파마(Evaluate Pharma)가 17일 공개한 분석보고서에 따르면, 2014년 매출액 상위 10대 의약품 가운데 생물의약품이 1위에서 6위까지 휩쓸고 9위 품목을 합하면 총 7품목이 생물의약품이다. 이는 2008년 5품목, 2000년 1품목과 비교된다. 아울러 2014년 매출액 상위 100대 의약품 중 생물의약품이 50%를 차지할 것으로 전망되었는데, 이는 2008년 28%, 2000년 11%와 비교된다. 따라서 5년 후면 그야말로 합성의약품에서 생물의약품의 시대로 전환될 전망이다. 2014년 매출액 상위 10대 의약품은 다음과 같다. • 1위: 아바스틴(Avastin), 항암제, 단클론성 항체, 92억3200만 달러 • 2위: 휴미라(Humira), 류마티스약, 단클론성 항체, 91억3400만 달러 • 3위: 맙테라(Mabthera), 항암제, 단클론성 항체, 78억1500만 달러 • 4위: 엔브렐(Enbrel), 류마티스약, 재조합 제품, 65억8300만 달러 • 5위: 란투스(Lantus), 당뇨약, 재조합 제품, 63억8600만 달러 • 6위: 허셉틴(Herceptin), 항암제, 단클론성 항체, 57억9600만 달러 • 7위: 크레스토(Crestor), 고지혈증약, 소분자 합성약, 57억3900만 달러 • 8위: 스피리바(Spiriva), COPD약, 소분자 합성약, 55억5200만 달러 • 9위: 레미케이드(Remicade), 류마티스약, 단클론성 항체, 52억2000만 달러 • 10위: 글리벡(Glivec), 항암제, 소분자 합성약, 51억3600만 달러

5년 후 매출액 1위로 전망된 아바스틴은 현재 세계 최대 매출품목인 고지혈증 치료제 ‘리피토’(Lipitor)의 특허가 2011년 만료되면 2012년 최고의 자리를 이어받는다. 아바스틴은 지난해 10위에 불과했다.   2008년 매출액 상위 10대 의약품은 다음과 같다. • 1위: 리피토(Lipitor), 고지혈증약, 소분자 합성약, 135억700만 달러 • 2위: 플라빅스(Plavix), 항혈소판제, 소분자 합성약, 94억4700만 달러 • 3위: 세레타이드(Seretide), 천식약, 소분자 합성약, 78억2800만 달러 • 4위: 엔브렐(Enbrel), 류마티스약, 재조합 제품, 64억5500만 달러 • 5위: 디오반(Diovan), 고혈압약, 소분자 합성약, 58억2500만 달러 • 6위: 맙테라(Mabthera), 항암제, 단클론성 항체, 54억8100만 달러 • 7위: 레미케이드(Remicade), 류마티스약, 단클론성 항체, 52억9300만 달러 • 8위: 넥시움(Nexium), 항궤양제, 소분자 합성약, 52억 달러 • 9위: 프로크리트(Procrit), 적혈구증식제, 재조합 제품, 51억6200만 달러 • 10위: 아바스틴(Avastin), 항암제, 단클론성 항체, 48억1800만 달러 위에서 볼 수 있듯이 작년 매출액 상위 10대 의약품 가운데 생물의약품은 5품목이고 5위 안으로는 합성의약품이 4품목이나 된다. [출처] 5년 후면 생물의약품 시대 온다|작성자 메디타임즈

Guideline for Presentation Presentation about > Something about application of molecular biology techniques Team Work > A team will get the same mark! > Make your own team.. Time > about 20mins. PLEASE~ Other suggestions > Speaking rather than Reading… > Question and Answer… > pls, avoid too heavy contents

I Structure and catalysis Chapter 1. Foundation of Biochemistry I Structure and catalysis Chapter 2. Water Chapter 3. Amino Acids, Peptides, and proteins Chapter 4. The Three-dimensional structure of proteins Chapter 5. Protein Function Chapter 6. Enzymes Chapter 7. Carbohydrates and Glycobiology Chapter 8. Nucleotides and Nucleic Acids Chapter 9. DNA-based information technologies Chapter 10. Lipids Chapter 11. Biological membranes and transport Chapter 12. Biosignaling Lehninger Principles of Biochemistry 6th Ed

II Bioenergetics and metabolism Chapter 13. Bioenergetics and biochemical reaction types Chapter 14. Glycolysis, Gluconeogenesis, and the pentose phosphate pathway Chapter 15.Principles of metabolic regulation Chapter 16. The citric acid cycle Chapter 17. Fatty acid catabolism Chapter 18. Amino acid oxidation and the production of Urea Chapter 19. Oxidative phosphorylation and photophosphorylation Chapter 20. Carbohydrate biosynthesis in plants and bacteria Chapter 21. Lipid Biosynthesis Chapter 22. Biosynthesis of Amino acids, Nucleotides, and related Molecules Chapter 23. Hormonal regulation and integration of mammalian metabolism III Information pathways Chapter 24. Genes and chromosomes Chapter 25. DNA metabolism Chapter 26. RNA metabolism Chapter 27. Protein metabolism Chapter 28. Regulation of gene expression Lehninger Principles of Biochemistry 6th Ed