Books, Reading, Science - Recommendations

                I’m currently inspired by a thread I participated in elsewhere on the internet.  Yeah, I’m all over the internet.  I’m embarrassed.

                Moving on.

                The thread centered on “The 11^th Plague” by John S. Marr and John Baldwin.  I hadn’t read it and felt that I should immediately go out and do so.  I’ve heard some unfortunate things about the translations available, but the bioterrorism aspect makes me want to read it anyway.  I’ll report back.

                I’m a huge reader and will happily dive into a book on almost any subject.  I will regularly go into bookstores and just wander around until I find something interesting in the most shadow-y corner of untouched books.  Since I live in the city, this has occasionally required me to kick out necking teenagers or homeless dudes trying to sleep.  (“What is it about a bookstore that makes people think they can just lay on the effing ground? –Dane Cook).  I’ve read anything from biographies of Henry VIII to old sea stories (Mutiny on the Bounty trilogy is phenomenal!) to classics like To Kill and Mockingbird.    I only eschew romance novels (Nicholas Sparks makes me eyes bleed.  So does Emily Giffin, for that matter.  Sorry folks!)  But, I’ve read my fair share of both nonfiction and fiction books that are based on science and I wanted to recommend some here.

The Hot Zone by Richard Preston

                This book scared me half to death.  It’s graphic (in illness details) and true.  It’s about an outbreak of Ebola in the DC area.  I literally stopped halfway through because I was having nightmares about catching Ebola and dying within 24 hours.  My friends kept encouraging me to read to the end, but I flat out refused.  They did eventually tell me how the book ends, which I won’t reveal here obviously, but I can say that my fears were assuaged.  Slightly.

                The book discusses the Ebola and Marburg viruses in detail: all the way from origins, to infection details, and to bioterrorism.  If you don’t have respect for what a weapon a virus can be, then I highly recommend you read this book.  Remember – it’s a true story.

Jurassic Park by Michael Crichton

                I’ve mentioned it before and I’m clearly mentioning it again.  Jurassic Park is my all time favorite book.  I’m sure most people have seen the movie, but I highly recommend taking a moment and reading the story.  Books are usually better and provide so much more detail.  In this case, you’ll read more about the idea of messing with nature, science, and the far-reaching implications of scientific advancement.

                For those who aren’t familiar (do you live under rocks?), the story tells about scientists who were able to find DNA for many different species of dinosaurs, clone it, and then recreate the living animals.  The dinosaurs are set up in a park and, just before opening, paleontologists, lawyers, and a few cheeky kids are invited to see what this new age zoo is all about.  The visit has horrible results and brings up several topics worthy of discussion.  Far more animals make an appearance in the book than the movie, too – pterodactyls, anyone?  Read the book.

The Lost World by Sir Arthur Conan Doyle

                This book was a completely accidental find.  I’ve never read Sherlock Holmes (I know, I know) and can’t even tell you how I ended up in Doyle’s section anymore.  Regardless, I pulled out a book called “The Lost World” and thought that it was much too thin to be Michael Crichton’s sequel to the aforementioned Jurassic Park.  Turns out, Doyle wrote a similar story about scientists who travel into the unexplored forests and find a thriving colony of dinosaurs.  The adventurers want to report back to share their news, but of course, things don’t go as planned.

                Sir Arthur Conan Doyle is very interesting as a historical figure in science, as well.  He was contemporaries with very notable scientists and attended scientific meetings in addition to being a physician in his own right.  One day I’ll do a post about him!

Complications by Atul Gawande

                My family is entrenched in the medical field while I am more on the cell/protein/drug discovery end of medicine.  I have only the most rudimentary understanding of the human body systems and tend to find beating hearts or open surgery disgusting.  However, tales of medical mysteries are fascinating.  One of my favorite TV shows is Mystery Diagnosis on the Discovery Channel.

                In his book, Dr. Gawande tells the stories of five different patients and their odd symptoms.  Some have myserious causes (the pregnant woman who could not stop vomiting) and some are terrifying (I had never heard of necrotizing fasciitis before this book.  Look it up – it’ll make you cry.)  Patient privacy is maintained throughout, but you get a feel for the limits of medical science and have the opportunity to see medicine from the other side: that of the doctor himself.

A Short History of Nearly Everything by Bill Bryson

                I love Bill Bryson.  If you’ve never picked up a book by him, I highly recommend “A Walk in the Woods” and “In a Sunburned Country.”  You will laugh out loud at his writing, his misadventures, and his traveling companions.  His new book “Home” is currently taunting me from bookshelves at Barnes and Noble.

                His primary genre is travel writing (with the Appalachian Trail and Australia being the respective subjects of the books above), but he stepped outside the box to write “A Short History of Nearly Everything.”  He spent a tremendous amount of time reading, studying, and learning science to write this book, which covers everything from the Big Bang to evolution.  This isn’t dry writing, either.  Mr. Bryson tells everything with self-deprecation, humor, wit and true thirst to understand science.  My father borrowed this book from me and I haven’t seen it since.  I also haven’t seen Complications after lending that to him, either…

Brian Greene’s books: The Elegant Universe, The Fabric of the Cosmos and The Hidden Reality

                Most other scientists have a list of PIs (Principal Investigators: those boss people who run labs) that they aspire to be.  I have a list of writers.  Clearly, I need a career change.  But, I digress.

                I aspire to have the job of Brian Greene.  He writes books about physics in a way that invites everyone to understand.  He discusses String Theory, time travel, worm holes, black holes, and so much more.  I listed his three most popular books above.  I’ve personally read The Fabric of the Cosmos and my husband is reading The Hidden Reality.  Give them a shot and with an open mind.  He wants regular people (people like you and me who didn’t study physics) to see the potential of physics in answering some really interesting questions.  How big is the universe?  Can we go back in time?  

Honorable Mention: Stiff by Mary Roach

                I realized that if I mentioned Bill Bryson I could not skip over Mary Roach.  She has a similar style (dry, witty, funny) as Mr. Bryson and writes about varied topics.  I picked up “Stiff” from a display of Halloween books.  My sister took this one from me and I had to wrestle it back. 

                Ms. Roach discusses the many varied uses for corpses in “Stiff.”  Did you know they are crash test dummies?  Laboratory tools to study human decay and help detectives determine how long ago a body died?  The uses for a newly dead body are quite long.  Who knew??

Links for books listed above:

The Hot Zone: A Terrifying True Story 

The Lost World

A Short History of Nearly Everything

Stiff: The Curious Lives of Human Cadavers

Conferences and Cancer Cells, Part 2

                I preface this post with saying: read it slowly and carefully.  Look at the diagrams.  It’s interesting as long as you can keep track of the key players.  This is like what my husband said before we watched “The Departed.”

                “You have to pay attention or it’s not going to make ANY sense.”

                Enjoy!

**

People need money to live.  They use it to buy clothes, a home, food, cars, and anything in between.  The money that cells use is called ATP.  It’s a small molecule that holds lots of energy in its bonds that the cell needs to make proteins, replicate DNA, pass through the cell cycle checkpoints, etc.  

                People work to bring money home so how do cells make money?

                They break down glucose!  Glucose is specific kind of sugar that when broken down properly can give the cell a lot of ATP.

                Figure 21.1 is showing you, in very brief and simple details, how a cell breaks down glucose to make ATP.  It consists of three steps. 

The first step is called Glycolysis (literally meaning the breaking of glucose).  The final product of glycolysis is a molecule called pyruvate.

Pyruvate is then turned into citric acid.

Citric acid is then converted into several molecules before being turned back into citric acid again.  This is called The Citric Acid Cycle (TCA).

These first two steps generate two other molecules: ATP and NADH (from NAD⁺).  

The third and final step is called the Electron Transport Chain (ETC), which essentially turns NADH back into NAD+ and creates ATP.  This final step generates many more ATPs than glycolysis or the TCA alone.  This step also requires oxygen.

Figure 21.2 shows the same steps again with the important molecules highlighted in red.

                Healthy cells take in glucose and turn it into ATP all day long as long as oxygen is plentiful (we are breathing).  Think of this system as a nice 9 to 5 working man who consistently brings home money and can provide well for his family.

                Cancer cells, on the other hand, are greedy.  They want more money.  They want as much as they can possibly get.  Think of these cells as thieves, charlatans or con artists.  Cancer cells grow rapidly and to do so they need a tremendous amount of ATP.  The straight forward glycolysis to TCA /ETC just isn’t cutting it for them to grow the way they want to.  So… they change.

                Cancer cells accelerate the rate of glycolysis, which increases the amount of pyruvate and NADH around.  This phenomenon is named “The Warburg Effect.”  Increasing the rate of glycolysis ensures that more ATP is around in the cell (Figure 21.3).  

However, the cancer cells have a problem.  There is only a finite amount of NAD⁺ in the cell and if glycolysis is moving faster, then NAD⁺ is being depleted very rapidly.  To continue its high rate of glycolysis, the cancer cell needs more NAD⁺.  How does it get it?

It can wait for the TCA/ETC to catch up, but many times oxygen isn’t plentiful in tumors.  Maybe there isn’t a blood vessel there yet to carry oxygen to it.  Regardless, waiting isn’t for cancer cells.  They want a more immediate solution.

The cancer cells choose an alternate path: they turn NADH back into NAD⁺ by turning pyruvate into lactate*.  The details aren’t important, but what is interesting is that instead of pyruvate entering the TCA, it becomes lactate and isn’t useful to the cell for energy anymore.  

This means that glycolysis is running at top speed and pyruvate is being used up as quickly as it’s made.  

I said cancer cells are greedy.  They want as much ATP as possible.  Pyruvate isn’t available from glycolysis to run the TCA/ETC.  If they could just get some more pyruvate from somewhere, then they could get the whole slew of ATPs from the TCA/ETC as well.  

Where can the cell get more pyruvate?  Where??

By breaking down glutamine, an amino acid used to build proteins.  Cancer cells break down glutamine, turn it into pyruvate, and can now run the TCA/ETC again. This leads people to say that cancer cells are “glutamine addicted.”  The need the glutamine to keep turning into pyruvate so the TCA/ETC can still run and pump out lots of ATP in addition to the lots of ATP made by glycolysis (Figure 21.4).  The metabolism of cancer cells is quite ridiculous!

* -  Turning pyruvate into lactate is what happens in our muscle cells during exertion.  For example, if you are running and you start to feel as if you can’t go anymore, your muscles hurt or you just want to stop, this is because there isn’t enough oxygen around to allow pyruvate to turn to citric acid and run the TCA/ETC.  The cell changes its metabolism so it can still generate some ATP and keep you running, but it isn’t enough as if the TCA/ETC was running.  Eventually we tire and have to stop.

Glucose: a sugar molecule broken down by cells to make ATP

ATP: adenosine triphosphate, a molecule commonly referred to as the “energy currency of the cell.”

Glycolysis: the process by which glucose is turned into pyruvate.

The Citric Acid Cycle: aka TCA, part of metabolism that breaks down and recreates citric acid over and over again.  It also generates some ATP and NADH from ADP and NAD⁺.

The Electron Transport Chain: aka ETC, part of metabolism that makes a lot of ATP from NADH and recreates NAD+ for glycolysis and the TCA.

REFERENCES

Alberts et al. “Molecular Biology of the Cell, 4^th Edition.”  Garland Science, New York, New York. (2002).

Warburg O (1956). "On the origin of cancer cells". Science 123 (3191): 309–14.

Kim JW, Dang CV (2006). "Cancer's molecular sweet tooth and the Warburg effect". Cancer Res. 66 (18): 8927–30

Conferences and Cancer Cells

                “Where were you all week?”

                “I was at a conference.  In Maine.”

                “People go to conferences in Maine?”

                “No.  Scientists go to conferences in Maine.”

                “What’s that like?”

                What is that like?  It’s an experience.  If you ever feel that you miss your twin extra long bed, showering in flip flops, or that inexplicable joy that can only come with living four feet from someone you’ve never met, then I do believe it’s time you attended a scientific conference.

                I’ve been told, but am not sure, that many work conferences are large affairs.  Thousands of people pour into one (MAJOR) city, drink at bars, sleep in hotels, and do …something?... during the day.  I don’t know what other professions do, actually.  But I’ll tell you what scientists do!  We attend talks, listen to other people’s research, talk about our own research, and spend a great deal of time on our computers.  

                Unlike larger conferences, this one was small (~ 120 people) and focused on one particular type of protein.  Since it was small, no hotels for us!  We were boarded at a college and lived in dorms.  Bathrooms could be found at the end of the hallway.  Boys on one floor, girls on another!  Yes, the average age of attendees was mid 30s.

 Mornings consisted of breakfast (cafeteria-style.  If you aren’t ready to walk aimlessly around with your food hoping upon hope that some other strangers will let you sit with them, then you may not be ready for this), followed by three hours of talks.  No coffee in the auditorium please!

                Afternoons were free until about 5pm when fifty posters went up in the dining hall.  The posters were manned by their creators and people came around to ask questions and discuss the research.  Dinner followed (again, cafeteria style - you needed self esteem armor to eat) and then another three hours of talks. 

 

                We were set loose from science at 10pm to either hide in our rooms (me) or attend a cash bar/fusbal tournament in the (again) dining hall.  For the record, we were in a very small Maine town.  There isn’t anywhere to go.  The coordinators actually admitted later that the venue choice was purposeful – it keeps people thinking more about science and less about anything else.

                By day four of this lifestyle, when I had successfully phoned every friend I had ignored since graduate school, emailed my husband every small joke that came my way (including a fabulous list of gaffes said by Prince Philip – link at the bottom of this post), and perfected the art of undressing/showering/redressing in a stall the size of broom closet, I was ready to go.  I think I ran to my car.

                While I’ll be disparaging about the “amenities” and lack of private sleeping quarters, I’ll be positive about the research.  Not all scientists are meant to speak in front of a large room (easily determined by the number of open laptops in the audience), but the ones that can speak and explain their research well are very interesting.  

                This entire conference was focused around one protein in our bodies.  That one protein is supplying projects and questions to labs all over the world.  Its job is so complicated, multi-faceted and nuanced that we still can’t say that we know everything about it.  Isn’t that extraordinary?  

Think about Paris.  We all know where it is, how many people are in it, and can look at a map of it.  We can find its simple facts.  But knowing the city, understanding its history, its future, the certain je ne sais quoi (I know!  I’m so cheesy!) is another story all together.  The same is true of proteins.  We know things about it, but we don’t know everything.  The more we know, the more we can understand when things go wrong in our bodies and how to fix them.  That was what the conference was all about.

I learned a lot of interesting things while I was there, but I’d like to focus on one aspect of cancer cells I never knew about until this conference: The Warburg Effect and Glutamine Addiction.  To explain why these two things are cool will require a bit more space than I have available here so look for a second post either tonight or tomorrow!



Also, feel free to tell me about other professions and their conferences.  Are they good?  Bad?  Different?  Better?  Do you have to pretend to be in college again!? 

Prince Philip Funnies: http://www.dailymail.co.uk/femail/article-2001251/As-Prince-Philip-turns-90-relive-hilarious-gaffes.html

               

HPV: Treatment, Research and Discovery Thinking

EDIT: More about HPV vaccine updates found here.

This will be my fifth post concerning Henrietta Lacks, the women who died in 1951 of cervical cancer and also donated her cells to scientific research.  These cells gave birth to a new technique: tissue culture.  Today, tissue culture is thriving in nearly all laboratories, including my own.

                Her story is really two intersecting tales: first, she was a woman afflicted with cancer and second, those cancer cells were a secret goldmine to scientists.

                The first post (Henrietta’s Cells) was an introduction to her, her story, and the book written by Rebecca Skloot that spurred this blog series.  The second through fourth posts concerned HPV infection and how that can lead to cervical cancer.  

I tried to break the information down in a way that would make sense to someone not intimately involved in the medical sciences.  I started with HPV infection from the point of view of a patient (HPV and Personal Reasons), then went the next step lower to show how a normal cervix changes when infected with HPV (HPV: Transitions) and finally explained what is actually going on inside the cells that makes them behave differently (HPV: The Cell).  Working the other direction, you could say I showed you how the inside of one infected cell changes (HPV: The Cell), then how those cellular changes lead to tissue changes (HPV: Transitions), which finally leads to how your body changes and what doctors must do to correct the situation (HPV and Personal Reasons).  I covered this progression in a flow chart shown in Figure 20.1.

                Before moving on to how and why these cells were so important to research, I’d like to linger on what is going on inside the cell for one last post.

                I told you that HPV messes up the cell cycle – it stops a cell from moving through all the checkpoints and dividing safely into two healthy cells.  Instead, the infected cell moves rapidly through the cycle, divides whether or not major problems exist in the DNA and essentially sets up the proteins within the cell to behave incorrectly.  Incorrectly behaving proteins leads to big problems down the line, one of which is cancer.  Its main media for messing up the cell cycle are two viral proteins, known as E6 and E7.

                Two interventions currently exist for HPV.  The first is the excision of infected cells.  Unfortunately, it can be difficult to know if you’ve cut out every single infected cell, which means that multiple Pap smears are necessary following removal.  The second is only a preventative measure: the HPV vaccine.  Yes, the vaccine is a really nice development, but it too has limitations.  The vaccine only works against some strains of the virus (not all ~ 30) so it’s not 100% preventative and it also offers no treatment for anyone already infected.

                Wouldn’t it be wonderful if there were some kind of medicine you could give a patient that would specifically target infected cells and stop E6 or E7 from messing up the cycle?  Just as antibiotics attack bacteria in our body and kill it, wouldn’t a drug to stop HPV infection and limit its effects once we came in contact with it be a huge sigh of relief?  Wouldn’t a treatment for people who don’t have access to yearly Pap smears (cervical cancer is one of the leading causes of death in woman worldwide) be such a boon for women?  What about other viruses or diseases that humans are plagued with?  

                This is what many scientists are working on.  We’re looking, I assure you!  

                How are we looking?  

                This is where ingenuity, long hours, and intimate knowledge of proteins come in handy.

                I’ve explained protein behavior in past posts as “p53 tells the cell” or “E6 deals a deathblow to p53.”  I haven’t actually explained how proteins communicate with each other.  The primary method they use is contact.  Protein A must attach (or bind) to protein B in a functional way.  They must come together in space in exactly the right orientations and with exactly the right amino acids to make a true connection.  Think of it as the difference between standing in a large crowd and having hands accidently touch versus a business handshake between two parties.  Both involve hands touching, but only one is a purposeful act.

                In the case of HPV, scientists have been trying to find ways to keep E6 and E7 from doing their jobs.  What if you could find a little molecule (which is essentially what drugs are) that would specifically bind to E6 or E7 and change its shape?  Small changes in shape will have huge effects on whether a protein can bind to another.  The smallest change can keep E6 from being able to bind p53.  If it can no longer bind p53, then it can no longer knock p53 out of the game and the cell will not succumb to HPV's attempts to deregulate it.  

                These are the types of things that scientist think about.  We have to picture the whole scene, pick out vital parts that allow it to continue and then ask “how can we stop that from happening?”  It is the same question over and over again with different diseases, cancers, infections, and medical problems.  What went wrong; how do we make it not happen again?

                Obviously, this isn’t an easy task.  Many times if we stop one thing from happening, other things will happen instead.  Ah, the butterfly effect!  To quote Ian Malcolm, “A butterfly flaps its wings in Beijing and in New York, we get rain instead of sunshine.”  These systems within our cells are connected and everything exists in a delicate balance.  

                Finding a drug that can do exactly what you want it to do, have minimal side effects, and show reproducible results in a system as enormously complicated as the human body is a true needle in a haystack.  Proving the drug's effectiveness is equally arduous.  It’s not uncommon for a drug to spend ten years in clinical trials before ever coming on the market.  Science is patience, perseverance, hard work, and lots of money.  And the scariest part about it is that no matter how hard you work, the possibility of finding the needle is incredibly remote.

                Just some food for thought about the lives of scientists…

                My next post in this series will look at tissue culture!  I also have some posts lined up on beriberi in the Australian Outback and the joys that is a scientific conference.

References

Me, myself, and I

Spielberg, Steven. (1993) “Jurassic Park.”

HPV: The Cell (cont'd Henrietta)

               My apologies for not getting this next post up faster – I was preparing for the conference that I’m currently attending.  I have actually never attended a scientific conference before, but I’ll spare you the details of such an adventure until it is over.  In the next four days, I will attend more talks than I can really handle, I’ll present my own research (as I was invited to give a talk) and I’ll unroll the poster that is currently taking up space in the backseat of my car.   Yes, a poster.  Just like your second grade science fair…

                Lesions within stratified epithelia tell a doctor that something is wrong.  In the case of cervical abnormalities, it often means the cells within the lesion are infected with HPV.

                What does the virus do once it is inside your cell?  How does it make the cell stop differentiating?  How do those things lead to cancer?

                Okay; one step at a time.

                Let’s start with something called “the cell cycle.”  

                Cells divide.  I think most people knew that and I bet, if some of you reach far back, you’ll remember that the process a cell goes through to divide is called mitosis.  Mitosis is actually only one act in a four act cellular play.  The others are called G₁, S, and G₂.  The fourth, mitosis, is called M.  

                Pretend you are looking at a cell that is just about to enter mitosis.  Keep watching.  As mitosis proceeds, you watch as the one cell splits down the middle to create two smaller cells (called daughter cells).  The two daughter cells will now enter a stage of the cell cycle called G₁, where G stands for growth.  This is a time for the cell to build itself up in size, make new proteins, perform its duties, etc.  

                Eventually, a signal will come that tells the cell is has to prepare itself to divide again.  At this point, the cell will pass out of G₁ and enter the S phase, where S stands for synthesis.  What happens now?  The entire DNA molecule within the cell is faithfully replicated.  At the end of this stage, the cell will have two complete DNA molecules: one for each daughter cell.

                Following the S phase, the cell enters another growth phase, called G₂.  It grows a bit more and prepares itself to split into two halves.  

                Once the cell gets the go ahead to split, it enters mitosis and two daughter cells are born.  These two daughter cells then enter G₁ and the cycle repeats.

                It is fair to mention that for any being to live a healthy life, the cell cycle must be protected.  A whole range of checkpoints exist that the cell must pass correctly before it is allowed to move on.  If anything is amiss, the cell won’t divide and will instead stop to fix problems or, in extreme cases, kill itself.  The cell cycle is no joke.

                This cycle is summarized in Figure 19.1.

                I’m sure you are wondering what this has to do with HPV.  Let’s focus on three parts.

One: Why does the HPV target basal cells and not other cells of the epithelia?

                Remember that I told you in the last post (HPV: Transitions) that the cells sitting at the very top of the epithelia can’t divide anymore.  If the cells aren’t dividing, then they aren’t passing from G₁ to S to G₂ to M anymore.  Instead, these cells exist in a static state known as G₀.  However, the basal cells are still dividing and they are still passing through the phases of the cell cycle.

                This is important information for a virus.  The main goal of a virus is to replicate itself (Spanish Influenza, Part 2).  In order for the virus to replicate, it needs its DNA replicated, which can only happen if the cell it gets inside will pass through the S phase.

                Those upper protective cells?  No S phase them.

                Those basal cells?  Excellent!

Two: What happens after the virus infects the basal cells?

                I’d first recommend reviewing the post “Spanish Influenza, Part 2” to remember what is involved with a viral infection: the virus “infects” a cell by getting inside, hijacks the cell’s machinery (which had been making cellular proteins) to start making viral proteins, and the cell begins to fill with freshly made virus particles.

                HPV’s genome also encodes two proteins not involved (or not directly involved) in making new virus particles: E6 and E7.  Together, these two proteins work to mess up the cell cycle of basal cells.  In the shortest and most plain English possible, this is how they work:

                I told you that the cell must receive some signals and pass certain checkpoints to exit G₁ and enter the S phase.  These signals are highly regulated and only happen when the timing is correct.  However, if E7 is around, it mimics these signals and tells the cell it is fine to enter the S phase.  It acts as a complete charlatan and the cell, while wary, follows E7’s instructions.

                Luckily, the cell isn’t dumb.  It has safeguards in place to protect it from being unnaturally forced from one phase of the cycle to another.  E7 does raise the suspicion of the cell’s defenses and the commander and chief of the army, a little protein called p53!  (Cancerous Mutational Problems)  In response to E7, p53 would normally tell the cell something was up and to halt operations.  E6, however, is waiting and deals a deathblow to p53 to remove it from the game.  

                So what do we have now?  A cell that can replicate (E7 ensures that) and divide (E6 ensures that) without anything making sure it is doing so properly.  These actively dividing cells are moving all over the epithelia and leading to the green cells from Figure 18.1 (HPV: Transitions post) and visible lesions that your doctor can see.

                I’m sure you can guess that this spells trouble.  Lots of trouble.

Three: How does this lead to cancer?

                The cell cycle ensures fidelity in replication of cells, especially in the DNA.  Cancer comes from many places, but one of which is mutations in the DNA (Cancerous Mutational Problems post).  Without p53 or proper signals for the S phase, the DNA in an HPV-infected cell will quickly rack up mutations.  It’s only a matter of time before one of those mutations leads to a problem.

                There are other ways, as well, but that is beyond the scope of this post.  I just wanted to show how the virus is setting up infected cells for big time failures.  It’s like having a spy in your company or someone spilling poison into your nicely baked cupcakes.  Sooner or later, there’s going to be a big BIG problem…

Cell cycle – the series of phases a cell goes through that leads to cell division

Mitosis – the phase of the cell when it actually splits into two smaller cells

G₁ – first growth phase of the cell cycle

S – synthesis phase of the cell cycle, DNA is faithfully replicated

G₂ – second growth phase of the cell cycle

M - mitosis

Daughter cells – mitosis splits one cell into two; these two new cells are called daughter cells

G₀ – if a cell has reached a point where it will no longer need to divide, but its function is still needed, the cell will enter a state called G₀ – a permanent G phase that can’t lead to the S phase.

References

Suryadinata et al. Bioscience Reports (2010) 30, pgs 243 – 255 

Doorbar, J. Journal of Clinical Virology (2005) 32, pgs S7 – S15

Huibregste JM, Scheffner M, Howley PM (1993) Localization of the E6-AP Regions that Direct Human Papillomavirus E6 Binding, Association with p53, and Ubiquitination of Associated Proteins. Molecular and Cellular Biology 13: 4918 – 4927

Munger K, Howley PM (2002) Human papillomaviruses immortalization and transformation functions. Virus Research 89: 213 - 228