Binf 631

1. Binf 631 Don Seto Department of Bioinformatics and Computational Biology College of Science George Mason University @Manassas, VA USA dseto@gmu.edu; (703) 993-8403; BINF 631 “Molecular cell biology for bioinformatics” http://binf.gmu.edu/dseto/binf631/ Course Text: Molecular Cell Biology by Harvey Lodish, et al, W H Freeman & Co., 6th edition (2007) Format: three exams @100pts ea two student oral presentations @12.5pts ea three homework @25pts ea, question format from exam total =400pts Grading structure: 85%A, 70%B, 55%C **Strict adherence to the GMU Honor Code expected. ***email contact as per GMU e-addresses, unless you tell me otherwise. Purpose: Review and standardize molecular and cellular biology concepts as foundation for bioinformatics. Develop skills for analysis, understanding and presentation of scientific information.

2. Binf.gmu.edu resource

3. Escaping superstition • Flammarion Woodcut, 18th cent.? (1888 reference) • “A medieval missionary....found the point where heaven and Earth meet” • heliocentrism • flat earth • gravity • creationism CPurrington (Swarthmore)

4. Policies and attitudes affect you more than you know; ex., Cervical cancer can be caused by a common virus • http://tell-someone.hpv.com/ (Merck; 2006) • Human papillomavirus (HPV) • One of most common STI; >100 different types • CDC estimates 20 million Americans have HPV ‘06 • NIH: 5.5 million new cases reported every year • Cervical cancer- kills 4,000 US women every year • Genital warts • Cancer of the vagina, vulva, penis and anus • ACS (‘06) estimates 2,420 new cases of vaginal cancer in US; 3,740 vulvar cancer; 4,660 anal cancer • Recurrent respiratory papillomatosis (RRP) • (noncancerous tumors in throat) • Abnormal Pap tests

5. ....not required to follow the recommendations of its panel of outside experts, but... • Merck • Developed HPV vaccine • Gardasil against four HPVs • Two responsible for 70% cervical cancer • (HPV16 and 18) • Two responsible for 90% genital warts • (HPV6 and 11) • Under FDA review • Conservative groups opposed on the grounds that it would encouragepromiscuity. • FDA panel of outside experts to meet 5/18/06 to recommend to FDA • FDA is not required to follow the recommendation, “but usually does.” • Approved 06/8/06 • TX -very conservative- makes mandatory Feb 02, 07 • First state • Expensive: Three boosts; $360; five year effectiveness • SC Harrison, ‘02 • ‘Structure and Function of Macromolecular • Assemblies” • Hybrid technique of EM and X-ray crys data • Generates atomic model • Spatial relationships of coat proteins affect • host immunological response • Vaccine development

6. CPurrington (Swarthmore)

7. Who should be interested in biology (science) and why • Feb 14, 2006 Alan Leschner. CEO, AAAS • on Earth & Sky Radio program (Deborah Byrd and Joel Block) • “A new tension between science and people?” • Last 4-5 yrs, the relationship between science and society has seemingly deteriorated. • Encroachment or abutment of scientific findings onto issues of either core human moral values or issues of economic values. • For the scientific community, there’s a feeling of greater disengagement between science and society. • Rising tide of fundamentalism that is an overlay to their (the public’s) views of science. • Scientists believe that scientific truths have value. • “If the purpose of science is to tell us about the natural world and the way it actually is, we shouldn’t be saying, tell us about the nature of the world as long as we agree with it and so long as it doesn’t make us uncomfortable.” earthsky.org sciencedaily.com

8. Life....... • Chemistry/Biology • Cell Biology/Biochemistry/Genetics • Molecular Biology • Genomics • “Bioinformatics”/ “Computational Biology” • Systems Biology > all lead to and contribute to biotechnology, molecular biotechnology • “nothing is really new.....” ……limited by imagination and background • “There is grandeur in this view of life..... most beautiful and most wonderful have been, and are being, evolved.” -Darwin

9. 1975 1980 1990 2000 Biology: Science in Transition Genetic Engineering DNA Sequencing Human Genome Project Genetic Fingerprinting H. Influenzae C. elegans • Biology is changing rapidly from a data-poor to a data-rich science • New Fields: • Bioinformatics • Computational Biology Human Genome PCR DNA Chips Hah! ---> www.sciencedaily.com JGref04 Growth of Genome Databases

10. Transcription Translation Bioinformatics Addresses problems related to the storage, retrieval and analysis of information about biological sequence, structure and function DNA RNA Protein ATGCCTATGATA... AUGCCUAUGAUACUG... MPMILGY... • Nucleotide sequences, genes (DNA, RNA) • Amino acid sequences (proteins) • 3D molecular structures • RNA and protein expression profiles JGref04

11. Computational Biology Develops computational models for molecular, cellular, and large scale processes GENOMICS CELLULAR SYSTEMS TREATMENTS • Cellular signaling and metabolic models • Correlation of genomic data and clinical treatments • Genomic diversity in natural populations JGref04

12. Lecture 1, Chapter 1 • Intro to life • ….cells • Survey of course topics

13. Cells come in all shapes, sizes, functions…

22. Cells [and the world] are divided into two types

26. But, single cellular does not mean ‘simple.’

30. Cells [and the world] are divided into two types • …..exception!

32. Exception- What is a virus? • Mimi virus • LaScola, B......Raoult, D., Science 299: 2033 (03). • 1992 influenzae outbreak in UK • 1.2Mb • 1260 genes • 50 not seen in viruses previously • More genes than some bacteria • DNA, RNA and plenty of proteins • Can synthesize own proteins • “is, by definition, alive.” -D.Raoult [???] • “Giant viruses in the oceans: 4th Algal Virus Workshop” • J-MClaverie, Virol J., Jun05

33. Chemistry and macromolecules • Key to biology, life….. • Tools are essential to the understanding of these molecules • and of the rules governing them • Knowledge leads to questions leads to knowledge

34. What is life? [sorta...] Biologically active macromolecules

35. Bio-replicating blueprint

36. Interplay of pathways • Bio 1? Bio 101?? Bio 201?

38. Whole creatures, proteins, genes, genomes… (macromolecules)

39. Molecular biology and geography Continental Drift- “Pangea” • biological evidence; Alfred Wegner, 1911 • fossils of similar plants and animals of either side of the Atlantic • geologic separation vs migration/colonization • Hawaiian giant flightless goose ~ species from Canada geese, 0.5MYr ago • By DNA analysis • Mite harvestmen; first land animals, fossils in 400 MYr rocks • Localized range of <50miles; do not disperse well; • DNA profiles of populations~ continental drift • eg, Forida population not related to other NAm species • related to WAfrica species • Boyer, Gilbert, et al., 2007

40. Mutations: Phenotypes and the molecular basis of.... • Good, bad, indifferent • sickle cell anemia gene Hb- • Glu to Val • high-altitude variant Hb- • CCR-5, co-receptor for HIV • ‘96 recessive, resistance to infection • ‘99 fatal encephalitis/WNV mice • Germ-line vs somatic

41. What is life? [how is life]

42. metabolism centered around ATP

43. What is life? • size, shape, function, timing, permutations • stasis/glue, movement/metamorphosis • sensory • adjustments • growth and division • death

48. turn, turn...

49. The ‘first’ science: “technology drives research drives technology dri...

50. Classic cell biology expt • Single cell to 10 trillion cells • Movie clip