Wednesday, September 12th, 2012


Good morning!  Another stunning morning.  Dew on the grass, crisp, cool air, and blue skies.  The truth is, it was such a beautiful morning that I kept waiting for the most beautiful thing to photograph.  When I was riding up to my apartment in the elevator, I realized I hadn't taken a picture of anything at all!

That's ok, though - there will be more beautiful days.

One of the things I thought about this morning was the fact that finding balance in my life is a constant struggle.  I'm not sure how it is for other people, but for me it's always been difficult.  The way it goes is a little like this:

1.  30% of days - I have ideas for dinner, have the house clean, spend enough time with doggies & Brian, don't sleep in dirty sheets, read books unrelated to science, take weekend trips, and leave work early-ish (i.e. 4:30 or so), I exercise and think about exercising a lot.  On these days, I spend most of my time feeling guilty about not doing enough at work or not thinking about work enough when I leave, or not coming in on the weekends.

2.  10% of days - I am ridiculously productive.  "Golden zone."  Balance.

3.  60% of days - I'm bitter that I don't get to finish the books sitting on my bed side table because when I get into bed I just want to close my eyes and go to sleep.  Exercise is just something that gets crammed in and not properly enjoyed, dinner may be haphazard, floors of apartment are gritty and shit sticks to my feet but I don't have time to do anything about it.  I climb into my unmade bed at the end of the day and it's got grit and hair in the sheets from the dirty doggies jumping into it.  Work is hectic & I spend hours at a time without blinking either setting up experiments, sacrificing mice, staring at my computer screen, or reading papers.  I do not leave early - I stay late and come in early.  I realize the day goes by without my realizing it.  There is some odd assortment of food in the fridge that can't quite get made into a coherent meal using any combination. 

The hard thing about a PhD is that there's a funny attitude about it.  There are absolutely no boundaries to your personal life.  I love science.  I love talking about science, I love doing science, and I love reading science.  I love thinking about my project and how I could make things work or figure something new out.  It's creative.

However, you could think about it non-stop.  The expectation is that because it's a passion and not just like any other job where you work just to bring home a paycheck you should willingly spend hours at lab and think about science nonstop when you're not there.

The reality is, even though I love it, there's a lot of other things I love, too.  I shouldn't really have to feel guilty about pursuing those other things, because the only reason that work is perceived as "more important" is because someone else  (i.e. culture), tells me that it should be.

I'm not going to come up with the next life saving cancer drug.  I'm not going to win a Nobel Prize for medicine.  Why isn't walking my dogs and eating Ratatouille just as important as being a scientist?

The truth is, it is.  

 Tuesday, September 11th, 2012
Central Park East - 7:10am

Another beautiful Fall-ish feeling morning today!  As promised, welcome to Part III of What does Jen do at grad school? 

Part III:  What does this have to do with computational modelling, mathematics, and why would any governmental agency (i.e. the NIH or NSF) ever give you money to do something so esoteric?


Well, let's review first.  It's been a few days after all. 

We had established that Interleukin 2 is a "cytokine" or a messenger that goes between T cells to tell them to become activated because there is something dangerous around.  T cells, if you recall, are immune cells distinct from B cells that either kill virus-infected human cells or help B cells make antibodies to fight off pathogens. 

T cells express low levels of Interleukin 2 receptor and are surrounded by Regulatory T cells, which express higher numbers of the Interleukin 2 receptor.  This is to protect you from T cell activation when there's only low levels of Interleukin 2 around. 

When a T cell Interleukin 2 receptor senses a molecule of Interleukin 2, inside it's cell membrane it phosphorylates STAT5, which then goes to the nucleus and changes gene expression in 2 ways:
1.  Tells the T cell to make more Interleukin 2 receptor
2.  Tells the T cell to divide and make more of itself. 

Now, STAT5 is phosphorylated predictably in response to Interleukin 2 connecting with the interleukin 2 receptor.  

So, it's a little more complicated than this, but for simplicity's sake we'll say:

1.  For every molecule of Interleukin 2 that interacts with the Interleukin 2 receptor, 1 molecule of STAT5 gets phosphorylated.  Additionally, we'll represent it like this:

This is the part where most people take one look at an equation and say "NO WAY, José!"  You're not MOST people, though, right?  The fact that there are 2 arrows refers to the fact that nature isn't perfect.  Sometimes, Interleukin 2 and the Interleukin 2 receptor fall apart before they get the chance to make a molecule of phosphorylated STAT5.  Most of the time they stick together well and succeed in making a molecule of pSTAT5.  "K" is a way that we refer to "rate" in science.  Rate, like the RATE at which your car is going is measured in Miles per hour.  The K represents the "RATE" at which a molecule of pSTAT5 is either made (on) or falls apart (off).  So, a molecule of STAT5 may be phosphorylated at a rate or "k on" of 1 molecule per second and may fall apart at a rate or "k off" of 1 molecule every 5 seconds. 

So now, experimentally, we can measure how much pSTAT5 is in a cell and how much Interleukin 2 receptor it has on it's surface.  As I mentioned in earlier posts, we have trouble measuring the amount of Interleukin 2 that is in the lymph node at any given time.  It's technically difficult, which means that we haven't figured out an accurate way to do it yet. 

So, if we know how much pSTAT5 is in a cell, and the rate at which pSTAT5 either is made or falls apart, AND we know how much Interleukin 2 receptor is on the cell, we can calculate the amount of Interleukin 2 that the cell must be "seeing." 

Why would we want to do that?  Why would we want to know how much Interleukin 2 is in a lymph node at any given time? 

Well there's something else about this system that we only know from testing it "in vitro" or in a plastic plate where we put T cells and pathogenic stuff and see what happens. 

We know that the amount of pathogen (i.e. virus or bacteria or venom, etc...) is proportional to the amount of Interleukin 2 that T cells make (we can measure Interleukin 2 in vitro, but it's hard to measure it in a living animal).  That is, as amount of pathogen increases, the amount of Interleukin 2 that gets made also increases.  You can represent this with the graph below.

 

So, as I mentioned above, if we can calculate the amount of Interleukin 2 from the amount of pSTAT5 and Interleukin 2 receptor that are in the cell, we can also calculate the amount of Pathogen that was initially present.  

Cool.  

"But!!!!"....(you may say)....

"But can't you just count how much pathogen was in a body in the first place?  Can't you culture bacteria and viruses and stuff like that? Why do you need such a roundabout way to do something that can already be done?"

"YES!  You can." (I'll respond)  

What about autoimmunity?  What about Graft Versus Host Disease (GVHD) following bone marrow transplants?  What about Lupus?  What about Rheumatoid Arthritis?  What about Crohn's Disease?  What about Psorasis?  What about Rheumatic Fever following Streptococcus infection?  

There isn't really any measurable bad stuff from those types of diseases, but we have a LOT of T cell activation.  We have so much T cell activation that your body's own T cells are attacking your kidneys, skin, intestines, heart, and joints.  But if you culture an affected person's blood there's no bacteria and no viruses.  There's no parasites and no allergens.  But if the T cells are activated, there must be bad stuff there....

and we can measure it....by NOT measuring it.  

Just by knowing how much pSTAT5 and Interleukin 2 receptor is on the surface of T cells.  

Cool.  

I'll conclude tomorrow.  I hope this was clear.  It got a little more complicated today so if anyone has any questions don't hesitate to email me or text me!  

Have a great day!

 

Monday, September 10th, 2012

A mixture of yesterday and today in the Park

Good morning, friends.  I may be disappointing some people today because I am not going to blog about the remainder of my science project (aka grad school).  Why, you may ask?  Well, because I really felt inspired to talk about Autumn today.  

This is why I feel inspired to blog about Autumn today. 

It was glorious this morning.  The doggies were all full of piss and vinegar because it is finally cool.  Autumn is my favorite time of year - I enjoy every minute of it.  It reminds me of when I was a kid and I was finally getting to go back to school, see my friends, go to Staples with Mom & Dad and get new pencils and notebooks and stuff of that nature, see my class list, get my locker, and watch football games (I don't even really like football but I think because it's a corollary to Fall, I enjoy it).  It reminds me of the anticipation for what will certainly be a great year.  There are so many things to look forward to in a new year!

These are the other things that I like about Fall:
1.  Temperature
2.  Leaves changing color
3.  Leaves becoming crunchy
4.  Dark in the morning (I know - it's insane that I like this, but it makes me feel more special when I wake up).
5. HALLOWEEN - I fu*king LOVE to dress up in costume.  I LOVE to drink alcohol out of skeleton covered cups you get from CVS.  I LOVE to eat a disgusting amount of miniature snickers and milky way's.
6.  Pumpkin flavored things that you put in your coffee.  (Only way to make Starbucks palatable is to douse it with pumpkin-flavor).
7.  Boots
8.  Thanksgiving - Should be interesting.  Will be my first Thanksgiving in awhile as a vegetarian.
9.  Running in the cool weather and not feeling like I'm going to keel over at any minute.
10.  Parties - it's always better when you're not sweating.
11.  Anticipation of X-mas
12.  Tea - who wants to drink this wonderful beverage when it's hot as hell out?
13.  My half marathon!  - Happens on Oct. 14th and I've been training for a month now. 
14.  Figuring out what my ACE (qualifier) topic will be.  It feels like a long road ahead in terms of this project, but I know if I'm patient and continue to work at it, I'll have something good figured out by December. 
15.  Football.  - What the...?  I don't even know.  I don't watch it except for now and again, but somehow I like it.  I JUST DO!

*Anyone have anything to addddd?????

 I'd also like to thank you all for your nice comments about my science blog.  I've gotten a lot of positive feedback (he.he. that's a science pun), from you all about it.  I'm going to finish it in the next day or two so you'll get the last piece and the wrap-up.  

Have a great day!

FRIDAY! September 7th, 2012
Central Park East - 6:45am

Good morning!  Ready for installment #2 of "What is it you do all day?"

Well I present to you, lesson #2:  What does any of this have to do with Jen's research?

Well if you recall, we talked about basic cell biology in Part I.  When T cells in the lymph node sense that there is a pathogen present, they start making their signal to divide - Interleukin 2 - replicate, and then help the B cells make antibodies, which will contribute to getting rid of or "clearing" the pathogen. 

How do the surrounding T cells in the lymph node sense that there is Interleukin 2 around?  They have a specialized receptor on their cell surface that detects specifically Interleukin 2. 

Well, the next step is something that is often taken for granted in high school or even college level cell biology classes.  The canonical teaching ignores the fact that Interleukin 2 isn't magical and can't change gene expression just by landing on the surface of the cell.  If you were in a room with no windows, you wouldn't know it was snowing just by snow hitting the roof.  You would have to wait for someone to come inside and tell you that it was snowing! The same goes for our T cell.  There has to be a second messenger at the inside of the cell membrane that goes and tells the nucleus how to change it's gene expression once Interleukin 2 is sensed. 

That molecule is called "STAT5."  The name isn't important - what is important is that STAT5 hangs around on the inside of the interleukin 2 receptor that sits inside the cell.  By itself, STAT5 can't enter the nucleus.  However, once Interleukin 2 receptor senses Interleukin 2, STAT5 is phosphorylated, which permits it to enter the nucleus and change gene expression.  Phosphorylation is a common method of signalling in a cell.  Basically it means that a big negative charge was tacked onto the molecule, which changes how it behaves biochemically.  If I lose you, it's not a big deal - what you need to know is that if STAT5 is phosphorylated (we call it pSTAT5), then the cell is "seeing" Interleukin 2.  If not, then there's no Interleukin 2 around. 

There's one more thing I should mention.  We can measure the amount of pSTAT5 in the cell.  We can also measure the amount of Interleukin 2 receptor on the surface of the cell.  For technical reasons, it's a little more difficult for us to measure the amount of Interleukin 2 floating around in the lymph node. 

Now, what exactly does that Interleukin 2 and pSTAT5 tell the DNA in the nucleus to do?

Well, here's where things get interesting.  In biology and in life nothing is black and white and in the case of T cells, nothing is "on" or "off."  We don't run our bodies like molecular on/off switches because it's too easy for something to go wrong.  Rather, there is always a balance of on and off switches happening at the same time.  The signal that predominates is the signal that is sent. 

In your lymph node, there are a bunch of T cells floating around that don't actually contribute to fighting off pathogens.  These T cells are called "Regulatory T cells."  A man that works down the hall from me named Sasha Rudensky was one of the first people to discover regulatory T cells.  Regulatory T cells have a constant low number of Interleukin 2 receptors on their cell surface. 

Why do you think that is?


Are you thinking?........


In this case, the Interleukin 2 receptors on the surface of the regulatory T cells act as molecular sponges.  Interleukin 2 is an activating signal.  There is constant low level stimulation causing production of Interleukin 2 in your lymph nodes, but not always because there's an actual pathogenic threat.  It's because your body isn't perfect and sometimes can't tell whether parts of you are foreign or you.  If there is only a little big of Interleukin 2 around, the Regulatory T cells will soak it all up and prevent any helper T cells (T cells that help B cells make antibodies) from seeing it.  This is SO important because if your T cells just react to any old Interleukin 2 they see, then you'll be in a full blown autoimmune disease state.  In experiments where they depleted the regulatory T cells out of mice, the mice developed SEVERE multi-organ failure because their own T cells attacked every organ system they had. 

I didn't draw it in the above picture, but these regulatory T cells sensing low levels of Interleukin 2 will be phosphorylating STAT5 and we will be able to measure that.  The measurement of pSTAT5 will be low, though, because there is only a little big of Interleukin 2 floating around and interacting with Interleukin 2 receptors. 

However, if there is a legitimate threat, much higher amounts of Interleukin 2 will be made and it will saturate all available receptors for the regulatory T cell.  This will make some available for the activating T cells, which have fewer Interleukin 2 receptors in their resting state. 

Once the activating T cell finally sees Interleukin 2, it BLASTS, meaning it does 2 things:  First, it divides and makes more of itself.  Second, it makes more Interleukin 2 receptor.  (Remember cell division and manufacturing of Interleukin 2 receptor are all as a result of gene expression changes that happen in response to the signal from pSTAT5).  This tips the immune "ON" switch even further because now the activating T cells are both more frequent and have more Interleukin 2 receptors.  They can now go help B cells make antibody and fight off the threat. 

Now what do you think will happen when we measure the amount of Interleukin 2 receptor and pSTAT5 in the cells?  The measurement of both will be MUCH higher!

We can actually represent what happens using a curve:

That's all I'll tell you about today.  If you're confused about the curve, that's ok - I'll explain it more on Monday during Part III - "Ok I get it, but why would you ever want to know this?" 

Thursday, September 6th, 2012
Central Park East - 7:00am

Good morning!  This photo shows the flood clouds receding.  After all of that rain and gloom and humidity the past few days, today was a welcome cool & breezy change.  The sky of NYC was literally half covered with clouds and they were pulling back to reveal gorgeous blue sky and sun. 

Unfortunately I have to be in lab early this morning because I have some things to do.  This means that installment #2 of "What in God's Name Does that Girl Do in Lab and Why On Earth Would Any Governmental Agency be Giving them $$ to Do That?" will have to wait until tomorrow.  You'll get the third part of the trilogy either this weekend or next Monday. 

Have a wonderful, wonderful day!!!

Wednesday, September 5th, 2012
Central Park East - 7:15am

Good morning!  I'm thinking about doing a three part installment - a trilogy if you will - on what the project is that I'm working on right now in the lab.  Sometimes explaining what I do is difficult.  Once I was in a bookstore with a friend and the cashier noticed me speaking with my friend about my project, she immediately piped up and asked me what it was about.  Rather than excited, I'm sad to admit that these types of situations make me a bit anxious.  I have to immediately gauge what I think the person knows about science and tailor my story so that it is - hopefully - understandable.  This is where it gets tricky.  Assume they know only a little - you come off as patronizing.  Assume they know more than what they actually do - you come off as some sort of pretentious scientist - or even worse... since you lose them, your story is boring.

At dinner with Brian's family the other day, I was fumbling over my words trying to explain my project to Brian's Dad.  As I'm trying to tell my story, I'm thinking, "He was an organic chemist...am I explaining too much/too little?"  My issue is complicated by the fact that my project is part computational - meaning that I mention the words "mathematical modelling, programming, quantitative."  Those are typically "Stop listening now while you've still got the chance words."  Brian, to my surprise, chimed in and eloquently explained the overarching goals of the modelling side of my project in about 2 minutes.  I was surprised and impressed.  Brevity is always the right strategy to go with.

I'll tell you 3 short vignettes that comprise my overarching story right now in the lab. 

Part I - What the f*ck is a T cell and why should I care?  I forget what a cell is and what it looks like. 

Well, calm down, I'll tell you.

Your entire body is made up of cells.  Your dog's body is made up of cells.  Your basil plant on the windowsill is made out of cells.  Fishes bodies are made out of cells.  Insects and spider's bodies are made out of cells.  Bacteria are made out of a single cell.  Viruses are NOT cells.  You can't see cells with your naked eye - you need a microscope. 

Lets zoom in to YOUR cells.  Think of your cells as basketballs that contain a tennis ball (a nucleus), and that nucleus contains your DNA.  EVERY cell in your body has the same DNA, it's just that different parts of that code are being expressed at any given time to make parts of you unique - your heart is different from your stomach or your skin.

One important type of cell is the lymphocyte.  Lymph-o-cytes.  LYMPH refers to where they home and what part of system they are part of - the immune or LYMPHATIC system.  They circulate around your body and "home" to your Lymph nodes when you're sick.  That's why your lymph nodes swell up when you have an infection - they're full of cells.  "Cyte" is a suffix that stems from the Greek "cyta" which means "jar" or "container" and refers to cell.  The cell is a container for your genetic material that makes you what you are.  One type of lymphocyte is the B cell - B cells make antibodies.  When you get a vaccination, the goal is to make a B cell remember that bad thing that it saw because if it see's it again it will respond (make antibodies) faster than the first time around.  Think of antibodies as molecular glue - they glop up pathogens (bacteria, viruses, toxins, venoms), and make it easier for your body to get rid of them.

The other type of lymphocyte is the T cell.  T cells do 2 major things:
1.  They help B cells make antibodies.
2.  They recognize when your body's own cells are infected with viruses and they kill those infected cells so that the virus doesn't spread. 
Also an interesting little fact, T cells are the cells that are infected by HIV.  That is why people with HIV eventually develop AIDS - Acquired Immuno-Deficiency Syndrome and will die of infections secondary to the actual HIV.  The virus kills the individuals' T cells so that over time, they can no longer fight off infections.  People with AIDS get infections that no one with a healthy immune system would ever develop. 

When T cells are activated (realize that they have a job to do - get rid of an invading pathogen), they respond by replicating and making more and more of themselves.  One T cell might divide 5-10 times in the time span of about 3-5 days.  Your cells divide much slower than Bacteria - E. coli can divide once every 20 minutes or about 70 times per day!!!

How do T cells know they should divide, though?  How do they tell other T cells near them that they should also divide and make more of themselves to fight off the impending infection?  They make a signal and they secrete or push out that signal towards other cells in the immediate vicinity (the lymph node is where this all happens).  For T cells, that signal to multiply is called Interleukin 2.  "Inter" means between and "leukin" refers to lymphocytes - "between lymphocytes." 2 just designates it as different than other Interleukins (there are many).  Here's your drawing to sum up today's story.

That was short, right??

Have a great day!  Stay tuned for tomorrow's episode:  "What the f*ck does any of this have to do with Jen's research?"

Tuesday, September 4th, 2012

Good morning!  I owed you guys some pictures today.  The top picture is from my walk on Friday.  I couldn't figure out how to upload it to my blog from my iPhone.  The next one down is of Sofie and Bear's cousin, Lola.  Lola is Stefanie (Brian's stepsister), and Brandt's (her husband) dog.  She is a mutt but they think part "Nova Scotian Duck Tolling Retriver."  The next one down is of Sofie eating a green bell pepper that she found in Brian's Dad's garden.  Both she and Bear ate all manner of stuff that had fallen in the garden - peppers, cherry tomatoes, etc...The next two down are from today's walk in the Park. 

It was a beautiful walk this morning - it's starting to be dark again in the morning when I walk - which for some reason I really like.  It makes me excited and anticipate Fall.  It was also a bit rainy and very overcast so there was almost no one out.  I savor those types of days in the Park. 

This weekend we celebrated the end of summer at the Jersey shore at Brian's Dad and Stepmother's house.  For a lot of people, it's sort of a bittersweet goodbye to summer, but for me, it's a true celebration - the worst season is on it's way out and the best is on it's way in!!  I don't even like football very much but I'm psyched that it's going to be back on.  I'm psyched for everyone going back to school, and for the leaves to start changing colors.  More than anything else, I'm psyched for cool, crisp mornings that leave me invigorated, smiling at my surroundings, and seeing the steam rise off my coffee in the morning. 

I digress.

We had a great time down at the shore.  We ate great seafood, went to doggie beach and let the pups swim in the ocean with all of the other dogs.  We also saw that whole side of the family at a BBQ on Sunday (except Maggie & James :( :( :( ) and I drank entirely too many frozen margaritas. 

Well - it's time to shower and go to work! 

By the way, I've gotten a new phone number and in the process lost everyone's phone numbers.  PLEASEEEEEEEEE call me or text me so that I can add you to my list!  Everyone who reads my blog is nearest and dearest to me and I don't want to be missing your phone calls! 

Here's my new #: (646) 627-5838

Have a great one!