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 2014 whitney-public-talk Presentation Transcript

  • The Genomic Revolution; How Sequencing Anything and Everything Is Changing the Way We Do Science { C. Titus Brown
  •    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
  •  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”
  •  First, genetic investigation of fetuses in utero;  Second, tracking hospital infections;  Third, investigating global nutrient cycling. Three stories:
  • 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?
  • 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
  • A DNA. C G T
  • AGTCCA is different from CCAAGT! DNA is combinatorial.
  • This means that for a string of 10 DNA bases, there are over 1 million combinations! AAAAAAAAAT AAAAAAAATA AAAAAAATAA … DNA is combinatorial.
  •  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.
  • 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
  • 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.
  •  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.
  •  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?
  •  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?!
  •  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:
  • Questions at this point?
  • You have two near-copies of each string of DNA, or “chromosome”. Inheritance of traits.
  • These two copies are a bit different. Inheritance of traits.
  • One copy may carry a particular trait – say, albinism, or wet earwax. Inheritance of traits.
  • Non-albino This trait may not show up if you have only one copy (albinism). Inheritance of traits.
  • Albino But if it’s on both copies, it may have an effect. Inheritance traits.
  • Non-albino Albino Albinism occurs only with two copies of albino trait.
  • OK Very badly ill …many diseases work the same way.
  • OK Very badly ill Can we diagnose fetuses?
  • Amniocentisis is invasive. http://www.reproduccionasistida.org/evitar-amniocentesis/
  • Father’s genome Mother’s genome Child’s genome
  • Heredity and crossover. Thomas Hunt Morgan, 1916
  • Mother’s genome Father’s genome Children’s genomes (Only 1 in 4 will have trait.)
  • 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.
  • Good accuracy! Fan et al., 2012
  • 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!
  • 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/
  • Questions?
  • Methicillin-resistant Staph (“MRSA”) Wikipedia
  • 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!
  • Alice Enters hospital Megan Chris Bob Julia Hypothesis 1: broad transmission
  • Jason (carrier) Visits hospital Cathy Health care worker Bob Megan Alice Julia Chris Transfers from another facility Hypothesis 2: deep transmission
  •  Does it spread within facilities? or  Does it spread between facilities? How does staph spread?
  •  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:
  • Tracking transmission by mutations in the genome Ancestor Present strains
  • Strain relatedness Hospitals: Do staph strains cluster by hospital? Prosperi et al., 2013. Nature.
  • Strain relatedness Hospitals: Do staph strains cluster by hospital? No! Prosperi et al., 2013. Nature.
  • 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.
  • Questions?
  • Exploring the microbial unknown!
  • The Great Plate Count Anomaly: most microbes cannot be studied in the lab http://schaechter.asmblog.org/schaechter/2010/07/the-uncultured-bacteria.html
  • Depth Location Distribution of microbial archaea off of Hawaii; why so many, so deep? Karner et al., Nature, 2001.
  • 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?
  •  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.
  • “Primary pump” – CO2 sequestration in deep ocean Wikipedia
  • 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!?
  •    More emphasis on analysis rather than just data gathering. More exploration – “just sequence it”. More unexpected results! How is cheap sequencing changing research?
  •  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:
  • Great Prairie Grand Challenge --SAMPLING LOCATIONS 2008
  • 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
  • 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
  • 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)?
  • Titus Brown, ctb@msu.edu (Just google me.) Thanks!