2014 whitney-public-talk


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  • Please ask questions!
  • Down’s synrdome
  • Down’s syndrome
  • Contact.
  • Ammonia -> nitrite -> nitrate.
  • Larvae/stream bottoms 3-6 years; parasitic adult -> great lakes, 12-20 months feeding. 5-8 years. 40 lbs of fish per life as parasite. 98% of fish in great lakes went away!
  • Notochord cells present, do not intercalate or extend
  • 2014 whitney-public-talk

    1. 1. The Genomic Revolution; How Sequencing Anything and Everything Is Changing the Way We Do Science { C. Titus Brown
    2. 2.    Reed College, BA in Mathematics Caltech, PhD and post-doctoral fellow in Biology; Michigan State University, Assistant Professor in Biology and Computer Science. My background
    3. 3.  I’m still confused by almost everything, but in some cases I have a lot more detail to be confused about.  So if you ask questions, I may say “I don’t know!” (but may then guess).  Please! Ask questions! On “Expertise”
    4. 4.  First, genetic investigation of fetuses in utero;  Second, tracking hospital infections;  Third, investigating global nutrient cycling. Three stories:
    5. 5. Genome sequencing!! The ability to cheaply sequence DNA is an extremely exciting and fairly new technique; all three stories used this extensively. Why these stories?
    6. 6. 1. 2. 3. 4. 5. DNA, genomes, and sequencing; Story 1: genetics of unborn fetuses Story 2: staph transmission in hospitals Story 3: global nutrient cycling in the oceans My research, briefly! Outline
    7. 7. A DNA. C G T
    8. 8. AGTCCA is different from CCAAGT! DNA is combinatorial.
    9. 9. This means that for a string of 10 DNA bases, there are over 1 million combinations! AAAAAAAAAT AAAAAAAATA AAAAAAATAA … DNA is combinatorial.
    10. 10.  This combinatorial property matters because it means that DNA is an alphabet and can be used as a language – you can build “words” and “sentences” in it.  (Just in case you’re wondering, we still don’t really understand the language in detail, although we know a lot about it.) DNA is a language.
    11. 11. Every cell in your body contains about 6 billion bases of DNA, in a particular order.  This is your genome.  Almost every one of your cells contains the same 6 billion bases of DNA.  …and it’s what you pass on to your children.  DNA underlies heredity
    12. 12. Since your genome has 6 billion bases of DNA, it would take up about 1.5 million pages in a book -This book would be the architectural plans for you! DNA is a language.
    13. 13.  Sequencing your genome is the same thing as digitizing it – putting the sequences of bases into a format that computers can read.  Analogy: scanning in old photos.  Important side note: just because you can digitize it, doesn’t mean you understand it! “Sequencing” the genome.
    14. 14.  You can look for known words and sentences, to diagnose disease susceptibility.  You can compare with other genomes, to find out what words and sentences might be responsible for disease. Why is it useful to sequence your genome?
    15. 15.  The first human genome cost between $300m and $3bn dollars. That was in ~2002.  Today, you can sequence your genome for under $5000!  This decrease in cost lets us look at a lot more genomes!  …and the price is dropping fast. How much does it cost?!
    16. 16.  Knowing a particular genome sequence lets us look for known disease susceptibility, as well as helping us find “words” associated with unknown diseases.  We can do this for around $5000 per person. Summary of DNA:
    17. 17. Questions at this point?
    18. 18. You have two near-copies of each string of DNA, or “chromosome”. Inheritance of traits.
    19. 19. These two copies are a bit different. Inheritance of traits.
    20. 20. One copy may carry a particular trait – say, albinism, or wet earwax. Inheritance of traits.
    21. 21. Non-albino This trait may not show up if you have only one copy (albinism). Inheritance of traits.
    22. 22. Albino But if it’s on both copies, it may have an effect. Inheritance traits.
    23. 23. Non-albino Albino Albinism occurs only with two copies of albino trait.
    24. 24. OK Very badly ill …many diseases work the same way.
    25. 25. OK Very badly ill Can we diagnose fetuses?
    26. 26. Amniocentisis is invasive. http://www.reproduccionasistida.org/evitar-amniocentesis/
    27. 27. Father’s genome Mother’s genome Child’s genome
    28. 28. Heredity and crossover. Thomas Hunt Morgan, 1916
    29. 29. Mother’s genome Father’s genome Children’s genomes (Only 1 in 4 will have trait.)
    30. 30. Pregnant mother + Father (+ Fetal cells) Mother's blood plasma. Sequence plasma, mother, and father – then count. * Complication: between 1/10 and ½ of cells are fetal.
    31. 31. Good accuracy! Fan et al., 2012
    32. 32. So, it’s now possible (if not yet really cheap!) to non-invasively figure out the genotype of a fetus, by sampling parents + blood. Instead of one genome, sequence three!
    33. 33. DNA sequencing shows a lot of promise for diagnosing rare diseases. http://www.forbes.com/sites/matthewherper/2011/01/05 /the-first-child-saved-by-dna-sequencing/
    34. 34. Questions?
    35. 35. Methicillin-resistant Staph (“MRSA”) Wikipedia
    36. 36. Staph tends to attack soft tissue in people who are already ill.  Correlation between staph infections and hospitals/assisted care.  Staph infections are a problem!
    37. 37. Alice Enters hospital Megan Chris Bob Julia Hypothesis 1: broad transmission
    38. 38. Jason (carrier) Visits hospital Cathy Health care worker Bob Megan Alice Julia Chris Transfers from another facility Hypothesis 2: deep transmission
    39. 39.  Does it spread within facilities? or  Does it spread between facilities? How does staph spread?
    40. 40.  Sequence staph strains from within hospitals.  If transmission is within hospital, all the strains will look alike.  If transmission is mainly from outside, strains will be spread across hospitals. Approach:
    41. 41. Tracking transmission by mutations in the genome Ancestor Present strains
    42. 42. Strain relatedness Hospitals: Do staph strains cluster by hospital? Prosperi et al., 2013. Nature.
    43. 43. Strain relatedness Hospitals: Do staph strains cluster by hospital? No! Prosperi et al., 2013. Nature.
    44. 44. More than 80% of staph infections were newly acquired from nonpatients! Implications for prevention: focus on isolation from outsiders, not just patients. Conclusions: mostly from outside.
    45. 45. Questions?
    46. 46. Exploring the microbial unknown!
    47. 47. The Great Plate Count Anomaly: most microbes cannot be studied in the lab http://schaechter.asmblog.org/schaechter/2010/07/the-uncultured-bacteria.html
    48. 48. Depth Location Distribution of microbial archaea off of Hawaii; why so many, so deep? Karner et al., Nature, 2001.
    49. 49. Measurements + extrapolation suggest: 1/3 of cells in ocean are archaeal; 2/3 of cells in ocean are bacterial. Approximately 20% of cells are from one group of archaea. Distribution of microbial archaea off of Hawaii; why so many, so deep?
    50. 50.  Hints came from just sequencing “seawater” in 2004: “an ammonium monooxygenase gene was found on an archaeal-associated” section of genome. What are all these archaea doing!? Venter et al., 2004. Science.
    51. 51. “Primary pump” – CO2 sequestration in deep ocean Wikipedia
    52. 52. Current theory is that a majority of the nitrification in the ocean (a driver of this CO2 sequestration pump) occurs via these archaeal cells. What are all these archaea doing!?
    53. 53.    More emphasis on analysis rather than just data gathering. More exploration – “just sequence it”. More unexpected results! How is cheap sequencing changing research?
    54. 54.  We can generate a lot of data quite easily.  How do we interpret the data correctly, and efficiently? How do we correlate between data sets?  How can we do good biology in the face of these technical challenges?  My research is:
    55. 55. Great Prairie Grand Challenge --SAMPLING LOCATIONS 2008
    56. 56. Sea lamprey in the Great Lakes Non-native  Parasite of medium to large fishes  Caused populations of host fishes to crash  Li Lab / Y-W C-D
    57. 57. Tail loss and notochord genes a) M. oculata b) hybrid (occulta egg x oculata sperm) c) M. occulta Notochord cells in orange Swalla, B. et al. Science, Vol 274, Issue 5290, 1205-1208 , 15 November 1996
    58. 58. You do! Via: National Science Foundation (NSF); National Institutes of Health (NIH); US Department of Agriculture (USDA); US Department of Energy (DOE) Who funds all this research (including mine)?
    59. 59. Titus Brown, ctb@msu.edu (Just google me.) Thanks!