“Today was good. Today was fun. Tomorrow is another one.” -Dr. Seuss

Wednesday Stairs in Harvard Stadium

Summer in Boston has come to a close, and I’m certainly coming home to PA richer (in every sense of the word except for the financial one) than I left.  Thank you to all of my friends who have made my summertime special!  You know who you are.  The memories that are going to stick with me are the ones that I made with you guys.  Heads up also, I will track you down for a hangout session if I’m ever passing through your stomping grounds.  You have a home in PA too, or whichever state the wind blows me towards.

I just had a great time with my parents, who came up for the weekend and explored the city with me.  It’s my pleasure to award the 2013 RedBeard14 Boston’s Best Pig-Out Spot Award to the Windsor Dim Sum Café in Chinatown.  No worldly foodstuff is packed with as much love as those Chinese sausage biscuits.  After feasting, my parents and I marched around the city like tourists for 12 hours and finished our adventure at the observation deck atop of the Prudential Center.  There, we had a bird’s-eye, 360˚ view of the surrounding Boston area.  It was a beautiful way to end my stay.

The story of hTRM9 has taught me a lot.  I didn’t just get to learn about culturing human cells and investigating the effects that hTRM9 has on cancer, but I learned about things to consider when setting up any kind of experiment, thinking outside of the box, and how to work in a laboratory.  I am proud to have made even the smallest and most marginal contribution to the project, I am very lucky to have been able to do work with the people who will solve that mystery.  My work was only possible because of the dozens of hours of training and mentoring that I received from my lab mates.  Thank you.  Many of the Dedon crew are working 70 hours a week to work on these projects.  8 a.m. to 2 in the morning, every day of the week, you will find people doing science in MIT building 56.  I have the utmost respect for their efforts.

My thanks goes out to the Juniata Career Services office for making my internship a reality.

Okay, it’s time to wrap up.  Enough mushy stuff.  For the past 9 weeks I have lived and worked with amazing friends.  Thank you.  If you’re reading this, I’m sure we will be in touch.  Keep on keeping on.

Cheers,

Aaron

Time flies like an arrow, fruit flies like a banana …

You’re back, yes!

Wanted to give you an update while I’m waiting for my cells to stick to the bottoms of their little wells.  I think that the metastatic cancer cells don’t feel very obliged to stick to the bottom of the plate.  Their lack of stickiness has been a problem for my experiment; I can hardly count how many cells survive if they won’t sit still for me.  They are wanderers.  They are pesky.  Patience.  Coffee.

It’s so crazy that I only have one week left.  Time flies when you stay busy.  There are little things about this city that make it feel so different from Philly or NYC.  I noticed one when I hit up a free Bosstones concert in the public gardens a few weeks ago.  That’s right, FREE CONCERT.  That’s like a salt block for college students.  It was actually the culmination of a week-long free music festival, completely funded by ONE man.  The whole thing was straight from his pocket.  The Bosstones (have you looked them up yet? Come on!) led him out onto the stage after the show.  He was the sweetest old guy in his late-seventies.  He told us that the morale of the city was really scrambled for several months after the bombing incident this spring.  He was so inspired by the way the city banded together in the past few months that he wanted to thank everybody.  He did that by creating the Out of the Box music festival.  He told us that he loved us about seven times, too.  That will stick with me for a while.

I did a few early morning workout sessions with some “crazy yahoos” (their words) who call themselves the November Project.  They are #2 on Oprah’s list of “Things That Make You Say Wow.”  I said “wow”.  I said “oww” too when I climbed into bed that night.  Jokes aside, I think that was the only time that I was excited to run stairs.  I want to go back too.  Workout instructors can get really irritating sometimes, but that was not the case at all.  There was a ton of encouraging energy from everybody.  All of the exercises are scalable.  That means Olympic athletes and ex-couch potatoes can exercise at their own pace, side by side.  It happens too, without anybody being left behind.  So cool.  Maybe I can find a friend at JC to make me run stairs in the morning.  Anybody interested?!

I’m planning a trip to the Museum of Fine Arts this afternoon.  I hear that mummified bodies and samurai armor qualify as “fine art” in Boston.  My kind of town.

Okay, time to give the cells a peroxide bath.  Hit me up this week if you’re in Mass!  Hit me up next week if you’re in PA!  Thanks for reading.

Cheers!

Cell Biology for Moms

Hey Guys!

I promised my mother that I would give you guys clearer run-down of my project.  I’ve decided to plop down in the park, watch the swan boats patrol the pond, and run through it with you while a guy picks some Eagles songs on his acoustic guitar.  My part of the project has developed into a toxicology study of two cell types.  The first type of cells was taken from a biopsy of a patient’s primary colorectal tumor (in the lower bowels).  The cells are flat and oval shaped, just like the cells that line your intestines, skin, and other organs.  Another biopsy was taken of a metastatic tumor (a tumor that spread to a location somewhere else in the patient’s body; I don’t know where though).  These metastatic cells are very different from the cells of the original tumor.  They are more spherical than the parent cancer cells, they grow very fast, and there is some evidence that they are better at growing in low-oxygen environments.  We suspect that these metastatic cells are hardier than the original tumor cells, which probably allowed them to survive their trip to their new location and grow under more stressful conditions. 

One day someone discovered that an arm of chromosome 8 was chopped off in our line of metastatic cells, but not in the colonic tumor cells.  That opened up a whole box of questions for Dr. Dedon and his fellow researchers.  So many in fact, that several publications and multiple thesis projects later, many questions remain unanswered.  Is there something important lying in the area of chromosome 8?  Is there a regulatory gene in that area that suppresses the growth of the cancer cells?  Did losing a gene on this arm of chromosome 8 allow the metastatic cells to grow more quickly than the primary cancer cells, which have the intact chromosome 8?

There are no genes in that area of chromosome 8 that we know would have been important in suppressing the haywire growth of cancer cells, so people began searching for new regulatory genes.   Before I tell you what they found, I have to tell mom what I mean by “new genes.”  Bear with me.  Well you know mom is going to say, “New genes?!  I thought we finished sequencing the entire human genome in 2003!  Tell the NIH I want my tax dollars back!”  Well, when the human genome was sequenced, we identified about 25,000 regions that looked like genes.  We don’t know what all of those potential genes do, though.  Decoding the genetic sequence has allowed us to characterize genes which code for many of our structural proteins and the enzymes that allow our cells to live (and some that allow them to die, like the apoptotic genes which allow cells to undergo programmed cell death).  A lot of genes are not understood yet, and offer little clues to their purpose or function.  Still, there are other uncharacterized genes which have known homologs, meaning they look similar to stuff that we understand in other organisms.  In other words, we have a gene in humans, we don’t know exactly how it works, but we know how it’s genetic cousin works in yeast, or zebra fish, or something.

So what DO we know about the missing arm of chromosome 8?  Some familiar genes were found there, probably not suspects for regulation of cell growth.  Scattered among the known genes, there are a few uncharacterized ones.  By adding these genes back into the metastatic cells, one at a time, somebody found which of these uncharacterized genes was able to slow down the growth of the metastatic cells.  Adding this gene back into the metastatic cells slowed their growth back down to about that of the cells in the primary tumor.  The gene had a name, and the name had an 8-digit alpha-numeric code.  Email me if you’re dying to know.  Dr. Dedon gave it a better name, hTRM-9.  You’ll have to take my word, but it is a better name.  We do know that hTRM-9 looks sort of similar to a gene that has been studied in yeast.  The yeast cousin codes for an enzyme that increases the speed and accuracy of production of certain proteins in the yeast.  So how might the loss of the similar human gene, hTRM-9, confer some sort of hardiness to the metastatic cancer cells?  Let’s start by asking some more specific questions.  Does hTRM-9 make the cells more resistant to hydrogen peroxide, a molecule that damages our DNA under conditions of oxidative stress?  What about nitric oxide, a DNA-damaging chemical made by our immune system when inflammation occurs?  Can cancer cells without hTRM-9 grow better in the low-oxygen environment of a tumor?

This is where my toxicology work begins.  To answer our questions, I have to conduct experiments to compare the metastatic cells with and without hTRM-9.  To make this possible, somebody re-inserted the hTRM-9 gene back into the metastatic cells, which, as you remember, had previously thrown the hTRM-9 gene out with the bathwater.  These are now the +hTRM-9 cells.  As a comparison to the +hTRM-9 cells, the scientist also inserted an unrelated gene called Lac Z into some other metastatic cells.  Those +Lac Z cells should behave just like our normal metastatic cancer cells.  So now we can test the effect of the hTRM-9 gene inside the metastatic cancer cells by comparing the +hTRM-9 cells to the +Lac Z cells.  That’s my job.  I treat both types of metastatic cells, +hTRM-9 and +Lac Z, with hydrogen peroxide, nitric oxide gas, or low-oxygen air (shown below) to see if the presence of hTRM-9 has an effect on their survival.  If the +hTRM-9 cells die more easily than the regular +Lac Z cells, then we know why the metastatic cancer cells got so tough after the hTRM-9 gene was lost along with the missing arm of chromosome 8.  If the +hTRM-9 cells don’t die more easily, then we keep looking for other ways to treat them.  Hopefully we will find a treatment that illustrates the way that hTRM-9 makes the cancer more fragile!  We have to repeat the experiments multiple times in order to have substantial confidence in any conclusions that we make.  It will take some time in order to get a feeling of whether the hTRM-9 gene has a role in making the cancer cells more vulnerable to treatment.

With any luck, we will see something interesting!  Thanks for reading, guys.

(Below – The +hTRM-9 and +Lac Z metastatic cancer cells, while their air chamber is refilled with air that is  only 1% oxygen.)Image

 

Time to Digest

Independence Day was a good time.  We didn’t end up seeing the orchestra (apparently it was one of the gigs where people start pitching tents 12 hours before the event), but the fireworks show was one of the best I’ve seen so far.  My favorite deployed hanging strands of flares which hung from parachutes and drifted our way like glowing jellyfish.

We did an admirable job of covering the city over their 3-day stay.  I’m pretty sure we all had sore feet by the end of each day, which was satisfying. We visited Harvard Square, the docks down by the bay, and everywhere in between.  We had ravioli from the north end, Mr. Bartley’s burgers, fish from Legal Seafood, cannolis from Mike’s, and the local brew from the historic Green Dragon pub.  Needless to say, the food was a big part of the sightseeing.  I think I’m still full.

I put my cells in their hypoxic (oxygen starvation) chamber to sweat it out for the weekend.  It’s looking to be a pretty slow one for me, though.  I walked the 2 miles to Target to look for a new bike, only to find nothing under $280 with an aluminum frame.  I promptly walked home with 2 gallons of Arizona tea and an arm full of free bagels from Dunkin’ Donuts as a consolation prize.  I’ll probably use my free breakfast and stock of caffeine to explore some nooks and crannies of the school.  All of the academic buildings are linked by a network of underground passages.  A good place to start.

Live it up!

Family for the Fourth of July!

Hi All,

Today I’m squeezing in my HPLC runs and a few last experiments before my (hopefully) long weekend.  I hope my cells will behave while I’m gone.  My friends from school are going to drive up tonight and hang out for a few days! :D  It’ll be like having a family for the weekend!  I already have a little sight-seeing list for us.  First and foremost is going to be the MASSIVE fireworks show over the Charles.  I’m not sure if I want to find a roof to watch from or brave the crowds along the river.  If we do stay on ground level, I really want to go see the Boston Symphonic Orchestra at the Hatch Shell before the fireworks.  The only other problem is that 500,000 other people are going to want to see that too.  I’ll let you know later how that turns out.

Things are going okay in the lab.  Everything takes more time than you expect.  There have been zero exceptions to that.  I did run into some surprising opportunities lately.  Yesterday I did a training session for working with mice in the animal facility upstairs!  A postdoc on the floor below is pretty happy to have me agree to dose her mice with some DNA nanotubules (they are single-molecule nitric oxide markers for DNA damage), and I am excited to get to work with mice.  So yesterday I did a mouse training session and learned how to care for the mice, hold them, give them IP injections, and anesthetize them for short procedures.  It was a lot of fun, and I really want to go back for some of the more advanced training programs that teach you how to draw blood and do some simple procedures.

First, I have to change my cells’ media for the weekend.  Enjoy your 4th!  I hope you get to spend it with your family and friends.

 

Finally@mit.edu

The “PH” button in the elevator didn’t disappoint. It’s actually a glass-encased lounge area for the residents of my dorm, complete with a workout area, a kitchen, tv lounge, and rooftop patio. Needless to say, there aren’t very many places on this side of the river with a better view of Boston.

So I’m finally settled in!  I began work with the lab last week.  Well, the first few “work” days mostly entailed safety training and a slew of paperwork to appease the bureaucratic powers that be.  I’m well into my lab work now though!  I’ve been getting a lot of experience with culturing human cell lines.  Now I’m moving on to drug dosing and making survival curves.  At this point the experiments are more learning exercises than actual research endeavors, but the plan is that I’ll be able to use these techniques on the colorectal cancer cells to characterize our tumor suppressor gene (hopefully next week!).

I’ve also been recruited to work on a separate project in an E. coli system … and I thought that I had escaped the enchanting fecal fragrance of an E. coli incubator when I left JC for the summer. We’re looking at modifications to the different subunits of the ribosome.  I actually tried my hand at comparing subunits between some strains using HPLC.  You can see the signature of each subunit after it matriculates through the column, making it the coolest analytical technique I’ve used in a lab so far.

Cooking dinner has been a nice way to wind down after I get out of the lab.  Trader Joe’s has some pretty awesome prices for produce, which makes it affordable to experiment with making new foods.  I’ve been trying to get out and get a feel for the city in the evenings.  I passed through Harvard Square a few days ago and biked over to the North End to get a cannoli from Mike’s Pastery Monday night, stopping at MIT’s bar to watch some of the Bruins game.  Boston has a much nicer feel than other big cities.  It’s not as hectic and crowded as New York, and I’ve actually enjoyed interacting with people on the street.  It’s definitely a cool place to be.  There are runners going up and down the river constantly and many people get around by bike.  You can tell that it’s up on the list of “Fittest Cities in America.”

Lots of plans, both in and out of the lab.  I’ll keep you posted.  Keep in touch!

Up and running!

Hi guys!

I’m just getting my feet wet with the blog, adjusting the settings and such.  I’ve got a week and a half to prepare for my trip to Boston to begin my work at Dr. Peter Dedon’s lab at MIT.  I’m going to be working with Chen Gu, a Ph. D. student who’s probably only about 3 years older than myself.  I’ll join Chen’s research project on a human tumor suppressive gene KIAA1456, which seems to suppress tumor growth by boosting cell aging and stalling the cell cycle.  KIAA1456 appears to do this by indirectly increasing the presence of reactive oxygen and reactive nitrogen species in the cell.

That reminds me of some research I did for a biochem case study where I learned that a cellular recycling process called autophagy (self eating) can put the brakes on cellular aging and increase lifespan.  It seems that Chen’s tumor suppressor is stalling cancer cells by pressing the gas pedal on aging instead.  It’s really interesting to think about cellular aging as a process that isn’t just linear, but something that can be accelerated or slowed down by our environment.  Here’s a creepily provocative radiolab story (with some hilarious sound effects) about stalling the aging process:

http://www.radiolab.org/2007/jun/14/fountains-of-youth/

Anyhow, I’m excited to see what new lab techniques Chen has to share.  An MIT lab is going to be a whole new ballpark for me.