Below is a transcript of what Dr. Jacobs had to say to the summer students during his first visit with us.

In this talk, Bill talks about phage resistance and the opportunity to find rare mutants using microbial techniques.  Other central aspects of phage biology were also presented to the students. 

Began with student response with respect to Bill's question; Tonight we have to find out, which weighs more, E. coli or planet earth.  The answer is the weight of the E. coli would be greater than planet earth.  "Phages aren't the real limiting step."  Chiara: antibacterial agents?  Bill: making bacteria is a lot of work.  If you don't eat, you don't grow.  Bacteria exist that can grab Co2 out of the air and turn it into glucose.  They only need a salt media.  You think about the essential elements, you need sulfur.  What's in DNA? student: phosphate.  Bill: C, N, O...things you need, primarily water is what you need.  You can find this on the web site tomorrow.  how much of you is water?  I think 70%  ...did you guys go to Graham Hatfull's website?  Did you go to last weeks Science News?  So it's big numbers.  Student: 9 billion grams, is 10^21.  How many people on earth?  6 billion.  Bill:  I did my first genetic experiment when I was 8 years old.  I started to collect lincoln cents.  Did you ever get those whiteman books, ... since the lincoln cents have been minted, they have been minted in the phili, denv, SF mints...rare is the 1909 svdb...these initials are on the bottom, and if you go through the pennies.  pre 1984 pennies are pure copper, after 1984 have Zn.  Bill: when I was 8 years old, I wnted to get all these lincoln cents, so I went to the bank, mom/dad lent me 25$, and I went through the pennies 1 by 1.  We are going to do this next week, we are going to isolate rare mutants.  I didn't really understand genetics until I came to NYC.  until you walk down 5th ave...bact gen is just like nyc...anything that can happen will happen...any day of the year, somebody will be wearing XMAS tree socks...so when I went through the pennies, I still have hundreds of pennies, I would go to different banks and get 2500 more pennies.  pretty soon I've got the whole neighborhood doing this...and 207 trips to the bank that summer, I went through more than 500,000 pennies, and I still didn't have a 1914 d, a 1914 s or a 1914sdb, cause they are really rare.  I went back and did the math, and determined I would have to go through a billion pennies.  To pick and patch mutants, if 1 per sec could be done, how many seconds would a billion sec be?  Anyone with a calculator? (student's solved).  Students: 31.7 years.  Bill: even though I went through, more than 30 years to get my penny!  The reason why genetics is so cool is that we are looking for that 1 in a billion event.  There are just a few rules.  1)  Darwin was right...variation occurs.  the guy with the xmas tree socks is down in the city.  anything that can happen does happen.  secret to being a geneticist: can't spend 31 years.  we have to find a way to cheat.  Look at your D29 plaques?  You can actually read a newspaper through the plaques.  BXZ1 is more turbid.  D29 is a truly lytic phage.  It does not lysogenize.  Let me explain this later event.  People haven't done good estimates yet.  It is estimated since every mL seawater has 10^6 phage particles, that there are 10^31 phages on planet earth.  A lot bigger than avogadro's number!  This makes phages the most abundant lifeform in the biosphere.  These allow us to do all kinds of cool things.  Yesterday, student's asked if phages kept bacteria from growing.  Earlier work thought could use phages for therapy.  In fact, lot's of people continue to pursue.  Russian group: pseudomonas, in partic. people with CF, get Pseud infections on top of skin, in mucosal surfaces, russians have shown can treat pseudomonas infections with phages.  The goal of life: if goal of bacteria-->bacterium, or phage-->phages, if you kill all your host, this is a dead-end cycle.  Are phages alive?  Chris: Long pause.  I think so...  Bill: that's a hard question.  do phages undergo metabolism?  when they go into the cell, they replicate and metabolise just fine.  Sometimes they are alive, sometimes they are just alert.  Let's say you are a smallpox virus; if you want to stay around, you don't want to wipe out the entire human pop.  It is better to be like HIV...where integrate into the genome, a temperatre phage, like G12 or L5, has the ability to integrate into the bacteria which it is plaqued and it grows.  Phages have protein heads and shoot in their DNA.  The cell can either burst (lytic), or integrate into the chromosome, where they just go silent.  Just like HIV.  They can survive for a very long time, in the chromosome of the bacteria.  In fact, they can sense when it is time to get out.  If the bacteria species is going to die, they don't want to go down to.  They turn on and start forming lytic growth.  It is a brilliant strategey.  Bacteria aren't always growing.  When water dries up, they know and sense that it is time to shut down.  we don't want to waste E and kill if no nutrients.  if sufficient universe nutrients, massive media bottle in galaxy, could have more bact than earth mass in 24 h.  But not that much media.  Bacteria sense environment and regulate replication.  Huge amounts of nutrients when they grow.  M. smeg growing...by way...why is email address is dasypus10, tonights homework assignment is to figure out why I chose dasypus as an email address.  Yesterday, were asking about college.  I always liked sci, but in pittsburg, football is big, and i never mean to be rude, i have genetic ritis pigmentosa, limited peripheral and nightime vision.  I trip over stuff.  Because of this, I couldn't play football, but I was a legendary football equip manager.  Univ Pitts, recruited Toney Dorsett, heard I was at Pitt, they put me on scholarship as equip manager.  I traveled with pitt jun varsity, and i spent a lot of time in football room, wasn't learning anything, I left pitt.  Great relationships, but went to edinburough state college, south of eerie pennslyvania.  teachers college, 20 mi s great lake, lot's of snow because of lake.  147 in average/year.  counted on 3 or so 2' snowfalls, wouldn't see ground oct to april.  math mjr, like micro.  i was amazed by lactose operon. 

E. coli ; glucose and saltes; nh4, po4, so4, Na, K....smallest bacteria has about 1700 genes.  mycoplasma are the smallest, 1700.  E. coli about 4000.  What kind of genes do you think it encodes?  reproduction, fission, involved in replicating it's DNA.  How about RNA?  (RNA polymerase) Need RNA to make proteins.  Chiara: do you make amino acids?  Amanda: other traits, like how big it is?  Bill: cool...some bacteria like bacteriacocci and streptococci...these are circles.  mycobacteria are rods.  other bacteria, like syphillis are spirochetes, and are coils. (board drawings).  Kristen: Kreb's cycle genes.  Bill:  that's right, metabolism.  I'd say all of life has many of enzymes of Kreb cycle.  Steve: genes from other evol stages?  Bill: yes, but evol selects against these.  Blake: cell wall genes.  Bill: complex, correct.  lipids, crosslinked structures, turns out bacteria cna adapt to diff sorts of grwth conditions.  NH4 taking up not simple.  nitrate turned into NH4 and grabbed; not a simple thing to do.  not simple to grab phosphate.  or from dirt, S.  need sp enzymes.  E. coli can eat diff C sources.  What is primary sugar in milk?  Lactose.  Do you know what lactose is?  it is 2 sugars.  Gluc, Galac.  Chiara: doesn't taste sweet.  Bill, very good.  sucrose is sweet; Lactose is just gal and gluc...glucose is like money in the bank, most of life at this point; we may find this not to be true in 5 years, but Gluc is typ the bread/butter all life likes to eat.  If you want to make gluc from galac, you have to break this bond and this will give you gal or gluc.  An ezyme recognizes this bond and cleaves it, this is B-galactosidase.  Now, you have 4000 genes.  Do you think you express them all? students, no.  Geuss how many genese e.coli in salt and glucose expresses?  Bill, 1500.  What happens to the other genes? Kristen: not needed.  How many genese in your body?  Being debated, 30-120 k.  Is gene regulation.  If you put e.coli in glucose, it does not want to turn on B-galactosidase.  Kristen: if we all carry the same genese in our bodies, brain cells don't reproduce.  How about in other places?  Bill: this is why stem cell research is underway.  you understand that it should be possible to clone people.  Steve: problem might be chromosome division.  Bill: yep, lot's of problems.  Steve: how does body specialize tissues?  Bill: stay simpler...Mernot got noble prize for this operon...this stupid e.coli (hamburger vrs. cheesburger)...in presence of galactose, turns on b-gal, w gluc, it's off.  How does it do this?  We know DNA (drew Lac operon)...we know is a seq of A,G,C,T...celery has same A,G,C,T...but how put together determines if celery or cockroach.  Same for your phages.  Ants we are going to find.  All of life: functional units are proteins, different strings of amino acids.  DNA is like the book, transcribed into RNA, which is translated into protein.  = central dogma.  all of life has to do this.  DNA-->RNA-->PTN.  Enzymes are specific, gluc, etc, lactose.  LacZ is gene for lactose breakdown.  DNA seq in e.coli encodes B-gal mRNA.  if you take this enzyme and mix with lactose, boom, it breaks it down.  turns into gluc and gal from lactose.  typically in gluc media, this gene is off.  No gal around, so why need it on.  How can it sense whether it wants a cheesburger or a hamburger?  How does it separate?  CHiara: markers on cell wall that does this?  Amanda: block on the DNA.  Bill: both right...permease takes it apart, ... is a spec enzyme tht takes up the lactose.  without the enzyme, could typically get into the cell.  typically, this enzyme is off.  How is it turned off?  Turns out there is a gene next to B-gal operon, called LacI.  This encodes a repressor.  A repressor is a protein that sits on the promoter, it sits on the promoter, is where RNA pol wants to go, but it can't go through this promotoer.  That protein is a physical block that shuts down the RNA pol.  Here's what is amazing: if Lactose gets into the cell, the sugar lactose can bind to this repressor, changes the protein.  If the Lac binds to that protein, it changes the shape of the protein so that it falls off the protein.  If the cell senses lactose, it binds to the repressor and changes shape.  The B-gal gene is turned on.  Can sense the presence of lactose by binding of a molecule to a protein.  30 k genes in a cell, you have no more than 1k expressed at one time.  And liver is a diff set than heart, neurons, etc.  Majority of time, don't want them all on.  Want to regulate.  How did they find?  Did we have an idea of the repressor?  It sounds as if you understand central dogma.  I tutored microbiol in college, and students didn't get central dogma.  if don't we'll learn about that, it's ok.  in fact, i'll show you some proteins, we'll talk about different proteins.  Really important things in life are proteins.  I'll talk more about the prediction of these tomorrow.  The first repressor ever identified came from a temperate phage.  if you are a phage, you don't want to be killing a cell, how do you want to do this?  temperate phages make repressors that shut down the phage genes.  menold showed this for bacteriaphage lambda...understood had to be a protein that prevented rna transcription.  Tomorrow: quiz on dilutions.  Not a simple concept, great job asking questions.  hope you are having fun.  you guys look at dirt differently, now, correct?  by the way, if you really want to find a phage, maybe you parents plant flowers, you know good dirt, and you smell, there is good dirt and not so good dirt, can almost smell it...when it smells good, it's not dirt, but bacteria that live in the dirt.  go home, do an experiment...find geraniums in back yard, there you will find phages ...where is all sun, bacteria are all dead.  Oh man, I can smell streptomycees...BXZ1... we will talk about this; I had these people from Africa, India, I'm interested if you find what dasypuss is tonight, this will give a clue what I am working on in the lab...phages are likethe cornerstone of what we do in developing new genetic tools; one of the things we do to rapidly diagnose TB, which can take up to 12 weeks in africa/india, one of things I did was engineer virus-->vector; new lifeforms; 1 gene to another.  Fire-fly luciferase-->phage.  makes light.  molecule-->photons.  Collect new fireflies, clone out new ffluxes.  If infected with a bacteria, see which antibiotics which to treat.  Culture strep out of mouth, culture, different antibiotics, problem with TB=12 weeks, slow growth.  With fflux-phage, glows in minutes.  Tb sample.  In 5 tubes; 1st=no drug, 2nd=rifampicin, now add phage.  No drug, it glows.  Drug kills, doesn't glow.  Binary, like computers.  Yes=on, No, no light.  Chiara: what probakaran was doing with GFP?  Bill, yes, but temperate phage...back to my africa/india...at edinborough, I thought was amazing e.coli could tell the difference.  in addition, when you understand dasypuss, where things i really work on, what really gets me excited.  people from africa, india...to go back and use it, 2 women: probakaran's boss, fellow put with someone, she comes in and says, bill, they are leaving this week.  We went to Bronx Zoo, which we will do next week, when walk past sealions, tigers, bears, and we got be zebra pit, I said we smell good dirt; put in my pocket and we left the zoo, and we isolated BXZ1...our first Bronx Zoo phage.  I used to think the zoo was cool, but what is cooler is all the microbes that live in the zoo.  We are going to get more samples going, is why collected other samples  at the garden. 

Tomorrow morning, I'd like to look at your plates, including your D-29 titer plates.