Arielle Tripp, Post 2

Greetings fellow young scientists,

I am very happy and feel rather fortunate to have had the opportunity to participate in a summer research program. My program is coming to an end, and so in a week I will be returning back to my home in California. Looking back over my last six weeks of research I am amazed at everything I was able to accomplish and learn within my lab. Also, I find it quite humorous how my initial project transformed and changed over the weeks of the program. Initially, we hoped to create a 3D model of the distribution of the targeted therapeutic CGM097 (an anti-tumor drug) through the use of MALDI mass spectrometry imaging. For the first month of my program I learned how to section tissue and thaw mount samples onto specially charged slides. Then I learned how to prepare matrix solution, a chemical used to dissolve and ionize sample tissue for later mass spectrometer analysis. Following matrix application, I learned how to use a mass spectrometer and interpret mass spectral data. All of which prepared me to repeat these series of steps on my “real” experimental tissue samples from mice intracranially implanted with cancer cells (which later developed into brain tumors, specifically gliomas). These mice had been treated with the anti-tumor drug CGM097, and so we set out to analyze how the drug’s effect on the brain, and the brain’s effect on the drug through the use of mass spectrometry analysis. However, the mass spectrometer broke and so the process was delayed. After the mass spectrometer was fixed, we ran our samples through the analyzer only to discover that the machine had not been calibrated properly. By this time my program was almost over, and so we decided to analyze what data we were able to successfully obtain from the mass spectrometer. The data was certainly unpublishable due to the incorrect machine calibration, however my supervisor wanted me to have the experience. So we analyzed the data and discovered that no drug signal could be detected whatsoever. Instead of mapping the 3D distribution of the drug we decided to instead map the distribution of two different lipids - one lipid expressed only within the tumor, and one lipid not expressed within the tumor. In this way we would still be able to create a 3D reconstruction of the tumor based on its lipid profile, rather than its location based on the localization of the drug within in the tumor.

 Currently, I am in the process of opening up all of the data files, which takes about 30 -45 min per files due to the fact that there is so much data within each file. After opening the files I will select the two lipids based off of the mass spectral data, and then save a series of images of each brain section. These images will then be put together in a software program to create the 3D image. Next week, I will present my project as a powerpoint presentation in front of the program and the various affiliated labs. In the future, I hope to submit my abstract for a conference or symposium. All in all I really enjoyed the experience because it was a great opportunity to do research different from my UCLA lab. At my regular lab, we actually handle animal husbandry and work closely with mice to conduct experiences. I appreciated how in my lab at BWH although we work with mice samples, we don’t actually handle any of the mice - this might be largely due to the fact that we don’t do any behavioral studies. I also enjoyed getting to shadow some of the other members of the lab as they went about their usual schedules. The lab is rather diverse in its experiments, and so I was also able to learn some cell culturing techniques.

In regards to HMS and the city of Boston, I love the culture and vibe of the people. There are people from all walks of life and from all over the world gathered here for the single shared purpose of scientific discovery and exploration. I feel fortunate to have been able to make my own small contribution to the greater of scientific and medical knowledge through my work done this summer.

There’s no place like home. I cannot wait to return back to California to see my family and friends.

-Tripp

 

This is a brief experimental schematic of how we analyzed drug ion distribution using MALDI mass spectrometry imaging.

Pictured is a view of Boston on a rainy day, viewed through a window in my lab.

Lara Roach, Post 2

Greetings from The Farm! I am now half-way through my summer here in Palo Alto. So much has happened since my last post! I have been working on developing a protocol for treadmill testing, which will provide functional analysis of the gene therapy approach developed in the lab for Duchenne Muscular Dystrophy. I will be measuring the time until the mice reach exhaustion before and after receiving a plasmid-based therapy aimed at rescuing the production of dystrophin missing in these diseased mice. I will also be performing a technique called eccentric contraction after the treadmill testing to determine the force the muscle can withstand. Since dystrophic mice have muscle degeneration and weakening, they withstand less force than wild-type mice. Our hope is that the gene therapy will increase dystrophin production and also the functional abilities of the mice to run longer and withstand more force. Since the gene therapy approach is plasmid based, involves site-specific integration into the genome, and can be delivered efficiently into muscle through a vein injection, this project is advancing the field of gene therapy for muscular dystrophy and could potentially lead to clinical trials in the future.

            Outside of lab, I have explored Palo Alto as well as San Francisco with the peers in my summer program. We had a barbeque for the 4^th of July, visited Fisherman’s Warf and Ghirardelli Square in SF, and saw Pixar’s Inside Out. Next weekend we will be travelling to Santa Cruz to explore the beach and boardwalk. I cannot believe the summer is already half over, but I am looking forward to making the most out of the next 4 weeks.

Until next time,

Lara

A video of a muscular dystrophic mouse running on the treadmill. I have optimized the running speed and will begin testing mice who will receive gene therapy.

Ghirardelli Square in San Francisco