Arielle Tripp, Post 1

MARC SUMMER BLOG, 

Greetings from Boston, Massachusetts. My name is Arielle Tripp and I am a rising junior studying Human Biology & Society and Neuroscience. Currently, I am conducting research in the Neurosurgery department at Brigham and Women’s Hospital as part of the Summer Training in Academic Research and Scholarship (STARS) program. My research is investigating the different pharmacokinetics (the movement of a drug into, through, and out of the body - what the body does to a drug) and pharmacodynamics (what a drug does to the body) properties of the drug, CGM097, on brain tumors within a mice model. CGM097 functions as an inhibitor of MDM2, aka Mouse Double Minute 2 Homolog. The MDM2 gene is an oncogene and plays a role in tissue development. The MDM2 protein functions as a negative regulator of transcriptional factor p53, a tumor suppressor. The protein expression of MDM2 and p53 is inversely related; an increase in MDM2 results in a decrease in p53 and vice versa. Normally, p53 functions as a powerful tumor surveillance mechanism; it regulates cell cycle, apoptosis, DNA repair and senescence. Mutations, however, can cause this system to go awry. For example, overexpression of MDM2 can result in cell over growth, tumorigenesis, and malignant transformation of cells. For this reason, MDM2 inhibitor drugs are essential in order to decrease its expression in cancerous tissue.

Therefore, my project is using mass spectroscopy analysis to do two things. First, we are analyzing the ability of the drug CGM097 to cross the blood brain barrier (BBB) and reach cancerous brain tissue. Secondly, once the drug has crossed the BBB, we are analyzing what its specific lipid and protein targets are within the cancerous tissue. The big picture goal of the project is to be able to develop a unique lipid and protein profile for brain tumors. Such a profile would allow a neurosurgeon, for instance, to take a sample of a patient’s brain during an operation and through mass spectroscopy analysis, evaluate whether the sample is cancerous or healthy tissue. This is amazing! One of the main obstacles remaining today in the field of neurosurgery is that during an operation often it is almost impossible to distinguish between healthy and cancerous tissue because they often look remarkably alike. Previously, the only way to view and locate the margins of a brain tumor was through continuous imaging; limitations of which included the possibility of cutting out healthy tissue, or leaving cancerous tissue behind.

Another big picture idea, more closely related to my project, is the ability of scientists to map within the brain the efficiency of anticancer drugs. Prior to the innovation of mass spectroscopy analysis of the pharmacodynamics and pharmacokinetics properties of drugs, there weren't very good ways to observe and empirically quantitate a drug’s performance. I don’t know much about technology used prior to mass spectroscopy for such analysis, so I will highlight its advantages instead. One of the great things about mass spectroscopy is that it allows you to create an image of a brain with localized signals, accurately depicting the precise location of a drug within a tissue section. In my next post I will go into further detail about how exactly a mass spectrometer works. For now, let me just say that the technology is quite fantastic. It allows high resolution imaging of every single molecule present in a tissue sample. Therefore, allowing a wide variety of lipids, proteins, small drug metabolites, and blood to be easily differentiated between. The applications are limitless, though I will discuss a few in my next post about the mechanism of mass spectroscopy.

In closing, I’m enjoying my summer research program. It rains every once in a while, but I don’t mind; it’s nice to experience rain after being out in the desert that is California for so many years. This post was supposed to also cover some aspect of my personal experiences outside of lab - I’ll make sure to touch on that in the next post. As well as, some of the clinical shadowing and other events I’ve been able to attend as part of the BWH STARS program. Wishing everyone a great summer. Best, Arielle Tripp.

 

Pictured are my roommates and I under the Harvard Medical School (HMS) sign. The BWH STARS is one of many programs run by HMS during the summer. Although only the four of us are pictured, my program has a total of ten scholars. Three of which are medical students, and the rest are undergraduates from universities across the nation.

This is an image of a mice brain section imaged with a MALDI- FTICR mass spectrophotometer.  The green signals represent the presence or drug, while the red signals represent the presence of blood.

Abel Ferrel, Post 1

MARC Blog 1

            I was a bit nervous about starting at my new lab because it was at the Harvard Medical School and it felt as if I needed to be at “the top of my game” to be able to keep up with my mentor. It turns out that the people in Dr. Harrison’s lab have been great. My first week was very welcoming. The members of the lab were very nice and we talked amongst ourselves to get to know each other more. We have designated “tea time” every day at 4pm where tea is literally made and it’s a break from all the lab work that you have been doing all day. Many members of the lab go to it including my summer PI, Dr. Harrison. He and I have spoken a number of times, mainly during tea time, about what I have done back at UCLA, how I have adjusted to Boston and his lab, and his history in research. In summary, the lab atmosphere has been awesome. Although I am the only undergraduate of the 20+ people here, I really feel like a member of the lab.

            My direct mentor has been patient with me as I have been working to get myself acclimated to this new field, but has a great sense of humor to lighten the mood. At UCLA, my focus was on muscular dystrophy; however, my field here is immune response and viral structural biology. That being said, the techniques here are very different from those I use at my home institution. It is molecular biology and biochemistry heavy here and we work primarily on cell cultures. Considering I have never worked with cell cultures, I was happy to see I did not contaminate my first culture. It addition to that, I am working on generating plasmid vectors to transfect cells and generate my proteins of interest.

            I have enjoyed my time here so far and look forward to the coming weeks. 

I'm excited to be working in this lab!

A sunny day in Harvard!

Luis Gonzalez, Summer 2014, Blog Post 2

Hello everyone it is Luis again and I just wanted to update everyone with what has been going on since the last time. I was able to use the b-galactosidase assay, shown below, to show that there is in fact a direct interaction between a-tubulin and g-tubulin. I was also able to identify a domain within g-tubulin, which is essential for this interaction to occur. The varying intensities of yellow correspond to the various versions of g-tubulin used to carry out the experiments.

This is the last week for the students who are only here for 9-weeks and therefore we are had our symposium on Wednesday and Thursday. Everyone had a great presentation and poster session and I really enjoy hearing about the research they conducted throughout the summer. It was an amazing experience and opportunity to meet everyone from the SSRP 2014 cohort, shown below, and I know for a fact that it will not be the same when I am here alone at Kairos the following week.

This summer was fantastic and I enjoy all of the group activities we had, which included a scavenger hunt in San Francisco, movie nights, barbeques, and social gatherings. I hope everyone had a great summer experience and cannot wait to meet all the new members of the MARC program.

Luis Gonzalez, Summer 2014, Blog Post 1

Hello everyone this is Luis Gonzalez a rising senior studying Biochemistry. I am currently funded through the HHMI EXROP program and I had the great opportunity to conduct my research at Stanford University and through their on local summer program SSRP. SSRP has great community of students and we have the privileged to be housed at Kairos, which houses all 33 students of our cohort.

Although it can get rowdy in afternoon, everyone single individual of the cohort is dedicated to his or her own respective research project. As for me I have the opportunity to work with Dr. Tim Stearns who is part of the departments of biology and genetics. The Stearns lab, which is found in Lorry Lokey shown below, focuses on understanding how the centrosome and primary cilium control cell function and influence development, and how defects in these structures cause a remarkable range of human disease, ranging from cancer, polycystic kidney disease, and obesity, to neurocognitive defects including mental retardation, schizophrenia, and dyslexia.

My specific project for the summer is studying microtubule nucleation and specifically to identify the proteins necessary for this event to occur. So a little background on the topic, microtubules are dynamic tubular structures composed of a/b-tubulin heterodimers, which are constantly undergoing periods of polymerization and depolymerization in order to alter their length in order to achieve their various roles. Microtubules play essential roles by providing structural integrity, transportation of vesicles and proteins, and most importantly the formation of the mitotic spindle, which is essential for the proper segregation of sister chromatids during the cell cycle. The organelle responsible for the formation of the mitotic spindle in eukaryotic mammalian cells is known as the centrosome, which is composed of a pair of centrioles, which are encompassed by pericentriolar material (PCM). The surface of the PCM is coated by ring complexes known as the g-tubulin ring complex (gTuRC), which based on structural studies of microtubules and the gTuRC have proposed microtubule nucleation to occur by a direct interaction of g-tubulin and a-tubulin. However the interaction between g-tubulin and a-tubulin has never been experimentally confirmed. Therefore the objective of my study is to definitively show that g-tubulin and a-tubulin interact and additionally to identify the residues involved in this interaction.

For my experiments, we decided to use Saccharomyces cerevisiae, which are grown in tubes shown above, as a model organism to conduct our studies due to the fact that all our genes of interest are conserved across all eukaryotic species. I made use of a technique known as the yeast two-hybrid system followed up by a b-galactosidase assay to quantify the strength of interaction between our proteins of interest, a-tubulin and g-tubulin.

Before I let you go I wanted to share a few images of the Stanford campus because it is a beautiful campus and bike friendly.

Benni Vargas, Summer 2014, Blog Post 2

Hi everyone! The CARE SEM SPUR Program has just ended and I have thoroughly enjoyed both the program events and the lab experience. I was very grateful for the seminars and workshops we have had. I took copious notes during those events because I knew that later on I will be asking myself, “What was that important thing they said during that workshop?”

In lab, we finally got our CFSE technique to work! After weeks of experiments that never seemed to work, we finally figured out that the concentration of CFSE dye that we have been using was too high. It was strange that our CFSE concentration was too high because in one paper we read, the authors used the same concentration and their experiments worked fine. We then used a lower concentration of CFSE and our experiments were working the way they should be.

There were many things I learned in my lab experience and one of them is time management. Reading scientific articles, analyzing data, preparing for the next day’s experiment(s), writing my research paper, preparing my poster and poster presentation, and all while working full-time in the lab has sharpened my time management skills. Seeing how my fellow lab members were constantly working hard made me want to constantly work hard too.

Although my summer research program and dorm residence contract have ended, I am currently commuting back and forth to the lab. I am looking forward to see what we will discover next.

Sam (my direct mentor) came to support me at my SPUR poster presentation!

 [³H]thymidine incorporation assay!

Richard Flores, Summer 2014, Blog Post 1 & 2

Blog 1

What's up everybody?! Me llamo Richard Flores and I'm a fifth year neuroscience major/theater minor. For my final summer as an undergraduate, I left sunny LA and flew across the country to take part in some exciting research in Dr. Michael Scott's lab.

Working for Michael Scott this summer has been a wonderful experience that has me excited for grad school. I do not know if I can say this but it felt similar to what a rotation in grad school might be like. Mike came up to me and ask me to pick up a project that no one has ever done and try to make it work. It's exciting to me to acquire a project that may not work, but if it does, would be a great new tool in the lab's arsenal.

I was attempting to develop a protocol for getting mice to smoke nicotine. Plenty of studies currently exist on the negative health effects of nicotine, the issue is that in most of those studies the nicotine is injected via a jugular catheter. This of course does not mimic the way humans utilize nicotine so developing a protocol that more closely resembles human smoking habits is needed.

Blog 2

In addition to this unique lab experience, I had the opportunity to meet great folks from all over the world. We were slow to link up at first but then ended up bonding strongly. I now have friends in Puerto Rico, Venezuela, and even random States like Ohio. The obvious advantage of knowing people from all over the country and the world is that if you ever find yourself in that state, say for a conference, or even if you feel like visiting that location, you have a friend there. Many of these good people I can now call my friends. I’ve already been asked to come visit Puerto Rico and Venezuela. The fact that I can visit those without having to pay for lodging is fantastic. Not only that, I’ll know somebody there that can intellectually stimulate me. Many of the nights that we all hung out we’d inevitably discuss science in one form or another. Even if we jokingly place restrictions like “no research talks allowed,” everyone knows we love science, and you obviously talk about your passions no matter what.

I have lived in Virginia before. When I last left, I vowed never to return. But this time was different. Because of my fun project and the variety of people I met, I see this place differently. I actually find it quite alluring now. In fact, I find myself considering the east coast as a potential location for grad school and life beyond that. This summer has indeed been eye opening.

When in Rome, you eat as the people of Charlottesville do!

You can beat the wild life of Virginia.

The scenery is almost too beautiful.

You really can’t beat the wild life. Just look at the colors of this cool little lizard!

Possible vampire lab

Our good ‘ol 3^rd President’s house. TJ also founded UVa, UVa Law School, and is the author of the Declaration of Independence. . . .No big deal.

Yea, I got to watch the Bruins play @UVa!!

Bruin spirit was alive and well!! (UCLA alumni 2005)

Mark Douglass, Summer 2014, Blog Post 2

Mark Douglass

08/29/14

Marc Summer Blog #2

This summer has been a whirlwind of excitement, productivity, and growth. I was able to learn so much from dedicating myself completely to lab life. I am more excited than ever to understand viruses on the molecular level. I worked independently, struggled though many troubleshooting phases, and as a result became a much more confidant researcher. I was able to synthesize a recombinant gammaherpesvirus with a tagged ORF73. This will allow me to transition towards experiments that will identify the molecular function of ORF73 within the context of a latent infection.  I hope to have significant results by the time I present at the SACNAS conference here in Los Angeles.

Within SPUR I thoroughly enjoyed the seminars and workshops we were exposed to this summer, and greatly appreciated the career opportunities that were showcased to us outside of the field of academia. I was able to gain much insight into my possible future as a future MD/PhD. Because of this program I was able met some incredible people, receive excellent guidance, and I was able to make some lasting friendships with future colleagues. I could not have asked for more.