WISE Words Magazine Mentoring Women in Science and Engineering [Winter 2010 Issue] Your Guide to Summer Opportunities Featuring:
• The Telomere Tales • Chronicles of a Lab Rabbit • The Princeton Women & Mathematics Conference
A Product of Women In Science Harvard-Radcliffe
3 5 7 9
Chronicles of a Lab Rabbit One Little Epsilon
The Telomere Tales A BRAINy Summer
National Oceanic and Atmospheric Administation Princeton Women & Mathematics Conference
National Oceanic and Atmospheric Administration Boulder, CO As a self-proclaimed theorist, infamous in high school for setting off fire-alarms in A.P. Chem, I’ve always intentionally shied away from labs, research, and the like. However, the spring of my sophomore year, I was awarded a generous scholarship through the National Oceanic and Atmospheric Administration’s (NOAA) Ernest F. Hollings Scholar program which provides term-time financial aid to undergraduate science and mathematics concentrators with a demonstrated interest in earth sciences. As a stipulation of the two years’ assistance, I was required to intern with a NOAA line office during the summer following junior year. When the Internship database was provided to the scholars in the fall of my junior year, I quickly scoured it for the most theoretical, physics-related work. And on June 1st, found myself starting optics-based research in NOAA’s National Geodetic Survey branch in Boulder, Colorado. The pace, rigor, and aim of the project appealed to me from the get go. I worked with an assorted team of NOAA affiliates -- including a Professor of Aerospace Engineering at the University of Colorado, Boulder, a senior IEEE theoretical physicist from Russia, and my mentor, Dr. Andria Bilich, alias antenna guru. Our project focused on extracting useful information from what is normally considered to be noise in GPS signals. Essentially, we studied what happens if GPS antennae receive, in addition to the direct signal from orbiting GPS satellites, signals that travel indirect paths. For example, signals that bounce off of the
Natasha Whitney ground or objects close to the receiving antenna. These types of signal disturbances are generally viewed as noisy and irritating by the GPS community, as they reduce the accuracy of GPS positioning measurements. But we were interested in investigating whether these perturbations might actually contain useful information—information such as the reflectivity of the surfaces off of which the indirect signals bounced. Specifically, during my ten week internship I was tasked with developing and conducting a control experiment to simplify several of the complicated, at times chaotic, parameters associated with analyzing these multipath errors. My time was divvied up between reading papers, texts, and books treating the underlying theory, field work involving the physical set-up and maintenance of the experiment, analysis of the resulting data, and model building in an attempt to marry the theory and the observations. It was the perfect combination, challenging and rigorous, while also being multifaceted and dynamic.
On a typical morning, I could be biking to my field site nine miles north of town in order to tweak my GPS antenna which was installed on a flat plateau reserved solely for government research, covered in summer wild flowers and framed by the Rocky Mountains to the West. Later that day, I could be discussing possible manifestations of electric field discontinuities and surface roughness in the data with a team member while strolling in the Flat Irons National Park that lay directly behind the office.
In addition to being visually stimulating, I found the work to be very intellectually stimulating. I felt my Harvard courses in optics, mathematics, and computer science had provided me with a smattering of analytical skills that came in handy-Fourier Transforms in some cases, Matlab experience in others-- and which enabled me to make solid contributions to the research efforts. Another key skill I benefitted from was an ability to discuss conceptually challenging concepts with my teammates and engage in cross fertilization of ideas--a skill honed by all nighters struggling with classmates to finish problem sets. Another beneficial lesson gleaned from those long nights at school was that often times it takes a fair amount of patience and time to reach an answer. My internship’s control experiment ended up being far more difficult than we had expected. I encountered a series of unanticipated glitches, both technical and theoretical, that obstructed any formal headway in attaining useable data. Only at the very end of my internship had I fine-tuned theexperiment sufficiently for us to begin to extract our long sought after results.
As a culmination of my internship, NOAA flew all Ernest F. Hollings scholars to the organization’s headquarters in Silver Spring, Maryland in order for us to present the findings of our research to our fellow scholars as well as to a handful of NOAA scientists. In addition to providing me with my first opportunity to present in a formal, scientific setting, the preparation of my presentation provided me with an opportunity to reflect on how much I had learned over the past ten weeks. The most profound lesson being that the path to an answer in scientific research is seldom straightforward or stress free-- in one particularly frustrating week during which my mentor was mountain biking in Scotland and subsequently offline, my GPS receiver, meteorological station, desktop video graphics driver and my sole form of transportation, my bike, all simultaneously failed. But learning how to maneuver past the road blocks, as I was forced to do this summer, in order to finally access the results I was looking for, was totally worth the ride. And after such an enlightening, interesting summer I’m eagerly anticipating continuing physics research in the future.
great opportunity for everyone to learn something, not just me : ) I was able to assist in the surgery, and next time I will carry out some of it on my own. We imaged with PET/MR - my first time seeing this machine in action. I was pleasantly distracted from my woe (refer to previous entry on the cuteness of rabbits) by the postdocs who joked about eating the rabbit once the FDG (F18-deoxyglucose, a radioisotope used in PET imaging) decayed in a day or so (the scans showed this animal’s prodigious muscles aka meat). It was a long day but, honestly, I could have stayed longer. Interesting fact: pretty much any lab animal except a mouse or a rat is considered a “higher being.” I wonder who decides that, and if it’s at all based on cuteness. My guess is, that it is. Rats and mice just get no love. How unfair is life !
Chronicles of a lab rabbit Boston, MA
July Already! 07/07/2010
As I slowly realize that there is a new month upon us and half of the summer has gone by, I am getting to appreciate the cool temperature of the lab. Sixty degrees doesn’t sound comfortable, but when the alternative is ninety seven outside, you learn to appreciate the lack of feeling in your toes (or other body parts if you’re one of those girls who wears skirts to lab, which is totally hazardous, by the way.) Spending over ten hours at work is good then because, not only do you miss the heat of the day, but you also get to know your colleagues, who are generally awesome people with loads of worldly knowledge to share. This has definitely been the case for me, and it’s been no trouble finding people as interested in watching world cup football !
I’m continuing to learn about the administrative details that make lab work possible. Being added to a protocol (so you can be authorized to access animal facilities, for example) can take forever, unless you are lucky enough to have a very efficient lab manager. As one of the fortunate few, my experience has been problem-free but I have seen others in really awful situations, particularly when they need something done fast. We ordered a rabbit for out next PET/ MR (magnetic resonance) project, and are expecting him tomorrow. I thought that I would be horrified to work with such an adorable fuzzy animal (who, in the end, must be sacrificed in the name of science). But then I remembered that in the summers of my youth in Belarus, I had no problem consuming them when they were part of dinner. So, should be aokay :) They’re still wicked cute though! **
Crazy Week! 07/16/2010
This week has been exceptionally busy ! On Monday we operated on and imaged my darling rabbit (I’m not attached to it, I swear.) It was so exciting to work on this pilot study -- no one had experience with this exact procedure so it was a
Yesterday I performed my first mouse surgery since 2009, and it was a great success. Stitching is still pretty tricky, and my stitches aren’t exactly beautiful yet - but they keep things together :) I am just glad that my little subject is bright, alert, and responsive (B.A.R. is a standard abbreviation used by the animal facility people as they evaluate the subjects.) The procedure involved some work with the liver, which is so incredibly sensitive... The capsule is very thin, and the organ itself is so vascularized that one wrong move can lead to massive hemorrhaging. That made me a little nervous. My teacher in surgery, Dr. Darsh, is the kindest, most patient woman in the world, which facilitated the success. I was hoping this summer would help me decide between medicine and research, and, so far, I am only more torn. Being on the cutting edge of research that directly affects medicine is so exciting, and endlessly challenging and rewarding. But working with patients and being able to help them directly has its own satisfaction... I am not sure that MD/PhD programs give their students enough time to work on complex theses. From what I’ve seen, most students are limited to two or three years to complete their PhDs before they must finish up the last two years of med school. Maybe by the end of the summer, I will have more insight :)
всех благ! (“all the best” in my native language) Until next time!
A Day in the Life: The PET/MR Edition 08/01/2010
The day of imaging is always stressful and hectic, as are the days leading up to it. There is much to be prepared, and, of course, never enough time to do it. 9:00 am - Radioisotope delivery to the lab. The FDG arrives under many layers of lead shielding to prevent unwanted radiation. Yes, there is such a thing as wanted radiation -- that which is used in our experiments)
As soon as it arrives, my mentor and I whisk is away to prepare doses of the exact number of curies (3.7*10^10 decays per second or a becquerel, which is the SI unit) needed for the experiment. Depending on the nature of that day’s procedure, we may prepare syringes of FDG with which to inject the animals, or we may soak adsorbent microbeads in the FDG solution to use as model tumors. Dose preparation is a painstaking process that requires rapt attention to prevent contamination of the surrounding lab areas. F-18 has a half-life of about 110 minutes, which makes contamination less of a huge deal (i.e., it’ll be gone the next day) but in general, it is good practice to keep things clean! We deal with small volumes and doses, but we keep our Geiger counter handy to survey the area after we finish preparing the FDG solutions. These instruments act as radiation detectors and have a helpful display and output a pulsing noise to help us find areas of contamination. 11:00 am - subject preparation. Once the doses are prepared and the area surveyed, we prepare the subject (last time, it was a rabbit). Because a rabbit is considered a higher being, it must be transferred to an operating room (mice and rats can be opened up in any procedure room, they do not require the “OR” label). There, anesthesia is administered and the animal is shaved. Not sure if y’all have ever shaved a rabbit before, but
Letter to the Readers Lovely readers, Thank you for taking the time to browse these “chronicles of a lab rat.” I’m a rising junior at the college, concentrating in biomedical sciences and engineering. I’ve been involved in clinical research for the past seven years, and I think I have finally found the perfect balance of physics and biology at the Mass General Nuclear Medicine and Molecular Imaging lab. Among the issues that I have (or will, undoubtedly) run into this summer are the ethics of injecting an animal with cancer, dealing with radioactivity, and finding time to study for the MCAT (i.e., adopting the motto of “ I’ll sleep when I’m dead.”) I’m now getting started on my second month of summer research. The project I’m working on involves developing a metric that will help us detect lesions on positron emission tomography (PET) images. PET scanning involves the use of radiopharmaceuticals to image the inner workings of the body, showing us things and taking us places CT and MR scans don’t go. Basically, we’re trying to find a way to non-invasively (read: without sacrificing the animal and taking out its organs) evaluate the uptake of the radioactivity by certain key organs. This translates into earlier detection of cancer. I won’t get into too much technical detail before we have a paper out, but I promise, it’s great stuff. I am very much indebted to my mentors at the lab, who have taught me all that I know. This experience would not be possible without them. their fur flies everywhere! They have a ton of fur on their neck that they pull out to use for their nests, so getting it all off was quite a production. After that followed intubation and the surgical procedure parts of our experiment. I assist in the surgery and learn as much as I can because next time I will be doing some of these steps on my own! 12:00 pm - Imaging, almost! The subject must be taken to the scanning bay and set up inside the scanner. This is simple enough for a subject who is conscious and can follow directions, but a sleeping post-op rabbit is a bit more complicated to deal with. All the monitoring equipment for the subject’s vitals are MR-compatible, of course, to avoid the kind of disasters where metal objects go flying into the scanner. The respirator stays in the room with the animal, while the monitors stay with the us so we can keep track of how she is doing and record her vitals in a logbook. 1:00 pm - Finally! Image acquisition begins, and can last for hours, depending
on the experiment. Someone is always monitoring the animal and manning the computer connected to the scanner. We take turns going for coffee and lunch, begin to relax a little bit. It is critical for the animal to be in good condition throughout the scan, so we are still kept on ours toes. We have access to veterinary support staff, who are wonderfully helpful and excellent resources for all our animal-related questions (like what a normal respiratory rate is for a rabbit). They facilitate all our progress, and supply us with all the necessary equipment to ensure the subject’s well-being, including the most thorough veterinary crash kit I have ever seen.
7:00 pm - Phew! Once the images are acquired, the reconstruction of these files begins (and this is a whole production on its own, requiring a different set of computer-savvy specialists) and the clean up takes place. There is the subject to be taken care of, the equipment to be returned, the records to be accounted for... Everyone is tired, but we leave with a sense of accomplishment.
One Little Epsilon
Who, What, When, Where & Why
Johnson City, TN Katie Banks
Reflection Phase I
So, everyone in my group has met with our professor several times, and we’ve all nominally started working on our problems–figuring out what we want to figure out about them, making conjectures and figuring out they are false after several hours of calculation, writing computer programs to search efficiently through ~2^49 matrices for counterexamples, etc. It’s a good day when I discover and can prove a formula for one case of the objects I’m counting. There’s a lot of literature review, too. I find the process comparatively relaxing–when I’m reading papers on what has already been done in the area surrounding my problems, I often feel like I’m building a mathematical toolbox and intuition that will help me approach the problems I want to work on. Diving in head first and tackling the problems naively can be fun, but it’s also daunting, emphasizing how much one doesn’t know when one starts work on a problem. Right now, I don’t feel like I have any traction on any of the problems I’m working on–so I’m mucking around: testing small cases in the rare event that they exist (the numbers associated to everything I’m working with grow super-exponentially! Unfortunate for my concrete-cases-loving, pattern-seeking brain), looking for recurrences (and then discovering that they do worse than the naivest of upper bounds I can establish), and brainstorming other angles I can take on the problems. All this is towards the goal of actually defining what those problems are, of course! I’m not in a comfortable place where I have a list of calculations or concrete angles I want to try out–still casting around. Which is sometimes one of the best parts of research, but also, for me, the hardest research skill to develop.
I’m enjoying the fact that the primary purpose of this summer for me is to work on math–that at this stage in my education and mathematical life, I don’t have to worry so much about what comes of that work. The doing, for now, is enough. I’ve approached and retreated from the frontiers of frustration several times over the past few weeks, defined and redefined what the heck I’m actually trying to do with these problems, bashed through lots of calculations to find that they are mostly inconclusive but suggest new directions. Doing math the last several years, I’ve learned to take at least a minute or two to savor the feeling of making a new discovery–since, most often, it turns out to be wrong, sometimes only in details and sometimes more fundamentally. Lately I’ve been waking up in the early hours of the morning with some regularity with thoughts that my proofs are wrong. Sometimes I actually get up to work through the details or check them out–and sometimes that even helps me be assured that I was, in this case, actually right.
Research is frustrating for everyone almost all the time, it seems. But right now, even with the frustration, it’s just so refreshing to not have the problem set and lecture grind. And to be able to spend time away from research problems reading up on interesting areas and techniques in mathematics and immersing myself in the culture and history of mathematics, as both profession and area of inquiry, a little bit more. I’m reminded why I wanted to study math in the first place, and that I want to continue to study it, wherever that may lead in the end.
The Princeton Women & Mathematics Conference Katie Banks
Princeton is the archetypal mathema-
tician’s town: quiet enough for deep thought and few distractions, and full of books, dearly-kept traditions and directionally-challenged people. It was both fitting and a little weird, then, to go to a conference on Women and Mathematics there--especially at the Institute for Advanced Study, a definitive icon of the traditional culture of academic mathematics.
The conference was for women, but as much about mathematics as the women doing it, unlike some women in science conferences that are more sociology. Each day, we had several hours of lectures and problem sessions relating to the mathematics surrounding the p-adic Langlands program, a central part of current research in algebraic number theory. But we also had lots of time, structured and not, to socialize and explore mathematical culture: we heard lectures from John Conway and explored Princeton’s math department (who knew John Conway has two offices, one he uses and one filled with colorful math puzzles and toys?) And, of course, we talked about women: there was a “Women in Mathematics” panel each day before dinner where older faculty spoke about their experiences related to a particular issue, and conference participants--a diverse group of upper-level undergraduates, grad students, faculty and post-docs-could join in the conversation.
What conversation was that? I think many participants, myself included, came in a little uncomfortable with the whole idea of talking about women in mathematics and uncertain what to say. The application process involved letters from people who could speak to your mathematical abilities and an essay about your favorite bit of mathematics, with only some checkboxes for if you’d taken any women’s studies classes and what issues you might be especially interested in related to women in mathematics. That was helpful: we were all assured that we’d be spending a substantial part of the conference doing mathematics, and not just talking about how we do it. But maybe it also contributed to our lack of creative questions for the panelists each evening. We’d ask, “how do you balance career and family?” and get answers that started with the awkwardly standard non-answer: “it’s hard, but you figure it out.” Some of the questions were difficult to ask and answer despite being standard: if you ask a question about how impossible it is to get an academic job because it’s worrying you, be prepared to be anxious about the answer you get. All that is not to say, though, that the panels were anything but useful and deeply enjoyable. For all that our questions are mostly the ones we have coached ourselves to ask, they are a useful sort of code for our true anxieties,
and the answers and discussions spoke to those after their tentative beginnings. When Lilian Pierce, a postdoc at the IAS, was asked what it was like to be a new mother and a mathematician, she talked about many of the common issues academics who are mothers seem to come across, and some of them are doozies. But her take-home message was “it’s awesome!”--despite all the difficulties she outlined, she wakes up most days excited to go do math and excited to come home to her baby, and with those joys as her foundation, the balancing--or rather, as she describes it, equally intense pulls-works out.
More useful than the answers we got to our questions were the answers to questions we didn’t know we had, couldn’t or wouldn’t put into words. With the combined experience and sensitivity of the women who’d been mathematicians for a while, we didn’t always need to ask what we really wanted to know in order to hear it--our worries were, after all, normal, and the words we used as gestures towards them time-tested. If the biggest question on our minds was “can I do this?”, whatever “this” was for each of us, the emphatic answer was “yes,” expressed in laughter-filled conversations over dinner, the recounting of the stories and battle tales of women mathematicians, or excited joint outbursts over solving a number theory problem. The beautiful, quiet campus is designed for thinking hard and well, and being surrounded by a community of women gave us support and extra enjoyment to that end. We were, some of us for one of the few times in our professional lives, far from the only woman in the math department room--and that is surprisingly comforting, even for those of us who don’t always notice when they are the only one. I would highly recommend the program to women with interest in mathematics.
The Telomere Tales Pullman, Washington The First Post 06/21/2010
Hello! Welcome to the developing account of a summer spent in a molecular biology lab in Washington state. This being the first post of my summer research blog, I suppose I will begin by explaining a little bit about my project.
I was very fortunate this summer to receive a Herchel Smith Summer Undergraduate Research Fellowship at Harvard, which has allowed me to join the lab of Dr. W. Chai of Washington State University. Dr. Chaiâ€™s lab studies telomeres, which are regions at the end of chromosomes that can be thought of as analogous to those plastic bits at the end of shoelaces. Telomeres are regions of repetitive DNA at the end of chromosomes that curl into special structures which prevent the cell from recognizing the ends of chromosomes as breaks in DNA. Generally, each time a cell divides, its telomeres shorten a bit until they become critically short, at which point the cell knows that it is time to stop dividing and senesces. In cancer cells (as well as in germ and stem cells), an enzyme called telomerase lengthens telomeres after each cell division so that the cell is granted some immortality. Telomerase is thus a beneficial enzyme when at work in germ and stem cells, but can be deadly when it is activated in cancer cells.
In the lab this summer, I am specifically studying one part of a tri-protein complex (called the CST complex) that binds to telomeres and is thought to control the length of the G-overhang, which
Annie Morgan is the part at the end of the telomere where one DNA strand (the strand that contains mostly G bases) is longer than the other. This G-overhang structure is critical to telomere function, as it tucks back into the double-stranded region of the telomere and forms a â€œknotâ€? that protects the end of the chromosome. The protein I am working with is termed the Stn1 protein, and its function as-of-yet is largely unknown. However, a study of the protein by Levy et al. in 2009 reported that two mutation sites in this gene are associated with longer-than-normal telomeres. Interestingly, both of these mutations create new phosphorylation sites in the protein product. A search of SNP databases online revealed that a third mutation commonly occurs in the coding region of this gene, so I am currently working with three possible mutation sites. My major project this summer is to insert these Stn1 mutations into cells and then analyze the effect of the mutation on telomere length. As I am beginning to see, though, this project is only the jumping-off point for many other inquiries that will beg to be explored along the way!
A Lengthy Update! 07/19/2010
This being only my second blog post, I realize I have a long way to catch you up on my research! So, here is a summary of what has been done so far this summer. As a refresher, the goal of my research is to study the mutations that commonly occur in a gene called Stn1, which binds to telomeres and is thought to effect their length. We would like to know the effect common Stn1 mutations have on
telomere length, and we propose to do this both by studying cells which already have the mutation, and by introducing the mutation into non-mutant cells and observing the result.
Orignially, we were interested in three mutations commonly found in the Stn1 gene. We sequenced many normal and cancerous cells, and found a relatively high incidence of the first mutation, a lower incidence of the second mutation (which is always found with the first mutation), and no incidence of the third (which we had suspected, as unlike the other two, it is a very uncommon mutation and has no documented effect on telomere length). From this, we decided to focus on the first mutation, although we will continue to study the second. Since deciding on this frame of focus, I have sequenced all the DNA I can find by designing primers to amplify the region of the gene containing the mutation, doing PCR reactions with these primers, cleaning up my PCR products and then sending them to New Jersey to be sequenced. Luckily, I had leared most of the skills I need for this process in LS1a during my freshman year at Harvard, and anything else was easy to fill-in on the go.
We were intrigued to find that tumor cells (which generally have longer telomeres) have a much higher incidence of our first mutation than normal cells do. However, a process called Telomeric TRF (one of many ways, all of which are relatively new, to measure telomere length) revealed that among tumor cells, those with the mutation did not have significantly longer telomeres than cells without, which means we did not find a direct correlation between the mutation and telomere length through this method of observation. However, interestingly, we found that normal cells with the mutation did have longer telomeres than normal cells without the mutation. This is a point of encouragement that perhaps our hypothesis of correlation still may be correct!
At the same time, then, I have been culturing cells in which I can introduce these mutations myself in order to observe their effects while controlling for other differences (in theory, this time, the cells should be identical but for my target mutations). The steps for intro-
ducing a mutation into cells are thus:
1) Make the mutant DNA by designing oligos that will replicate a DNA plasmid (circular DNA that contains the wildtype of my gene of interest) and introduce a mutation. Online software programs help a lot with this design!
2) Put this mutant DNA plasmid into bacteria cells that literally have holes poked in them by a CaCl2 solution (these are called competent cells). Grow this bacteria, and let it isolate the plasmid into its genetic material. Then, collect all the DNA from the bacteria and make sure you have your target plasmid in this DNA. 3) Apply this DNA to cells called Phoenix A cells that will uptake it and package it into viruses.
4) Collect the viruses made by Phoenix A (they very handily dump it into the media in which they live) and infect the target cells you want to study ( I am using two cancer cell lines, neither of which orignially have mutations in Stn1).
5) Grow the infected cells, and then check to make sure they are producing lots of your mutant protein by Western Blot.
6) Compare telomere lengths between cells that make mutant Stn1 protein and those that have not been infected. Today, I am doing my Western Blot of step 6 above. I have done Western before with the guidance of my friend in the lab Dr. Huang, but not alone. It seems to be working so far, but I hope it all goes correctly!
I am really excited to see if introducing the mutation will cause a difference in telomere length between cells that are otherwise identical. I will write again later to let you know what I find out!
To depart from the postings of methodology and results I have been writing, I thought today Iâ€™d include a short update on some of the non-research aspects of my lab! First, a brief introduction to the other members of my lab. Our lab has oper-
ated with five members for most of the summer, but we have a new lab tech who has just joined our group this week. The Primary Investigator in my lab is Dr. Chai, who is a faculty member of the WWAMI program and Washington State Universityâ€™s School of Molecular Biosciences. In our lab are also two post-docs, Dr. Dai and Dr. Huang, who were recently listed as the first authors on this paper (a very interesting one in the telomere field!) The other full-time member of the lab is Shilpa S., who is a Ph.D. student originally from Bangalore, India. All of the lab members have been a great help to me as I have learned to culture tissue, run different reactions, and navigate my way around the lab--I have been very fortunate that all the members of my lab are outstanding teachers. Now, I am playing a bit of that role as I help our new member, Cora, learn to preform her tasks in the lab. As she starts her first days of work, I can definitely empathize with her position as the green new member!
The Final Post 08/18/2010
Well, we have come to the last post of my summer research blog. Sigh. I cannot believe I am already finished in the lab-time has passed SO quickly. I feel like I have passed very quickly from knowing very little about telomeres (last winter), to reading everything I could on them and becoming fascinated but not actually expecting my own project (later last winter), to being a little freaked out but totally excited to design and take on my own project in the lab (beginning of this summer) to finally preparing all my results in a paper to publish (now!...a final version coming soon to this blog :] )
Another bit of newness to me is that I made my first lab presentation last Wednesday. Every other Wednesday, our lab members gather for a meeting in which we discuss general business and then hear a presentation on the progress of one memberâ€™s work, generally accompanied by a PowerPoint and heavy debate. I was a little nervous to present my work in front of the lab for the first time (how bad were they going to grill me?!) but the presentation went well, and it was a great opportunity to reflect on my trajectory for the rest of the summer.
If I have done anything important along this research process, it has been to ask questions. First, questions to myself: What do I want to do with my summer? Are there any research labs in Spokane? Then, questions to others: Can I come work in your lab? Will you grant me the financial resources to make this experience possible? Eventually, questions that could only be answered on the bench: Will a certain mutation cause telomeres to elongate? Why are we seeing a mutation more frequently in cancer cells than in non-cancerous ones? Finally, I hope these questions will find answers that will feed the larger questions that are being tackled all over the world: What do these results mean for the overall picture of telomere replication? How can we take translate these findings into cancer therapies?
As I write this, I am currently waiting for a ligation reaction to run (as a part of a molecular cloning experiment), and my timer is about to go off to send me back to the lab. More news later!
Thanks for reading!
Last Wednesday, another exciting occurrence befell the lab as film crews rolled in to take some footage of the lab at work. The paper (see above link) recently published from our lab in EMBO has gotten some local attention, so a news cast came in to interview Dr. Chai and film the rest of the lab at work. Drs. Chai, Dai, Huang, and Shilpa put a tremendous amount of work into said paper, so it is very exciting to see them getting positive feedback on their work!
Although answering questions is, intrinsically, the ultimate goal of a research process, I find that I am more interested in the future questions than in the results that have been generated by my experience. For those reading this blog who have not had a research experience themselves: ask some questions yourself! The expanse of what we have to learn even just about telomeres is so vast, my mind is boggled by what we have to explore in the wider fields of cancer, biology, and science holistically. There is definitely a place and a need for all inquiring minds to undertake research projects in any field of interest: all you have to do is ask!
A BRAINy Summer Atlanta, Georgia
Jessica Zuo Hello from the ATL! 06/20/2010
Hey everyone! I’m a rising sophomore spending the summer in Atlanta conducting neuroscience research. I’ve been here for nearly 4 weeks now, so here’s a summary of the program itself, and what I’ve been up to: The Center for Behavioral Neuroscience has a program for undergrads called Behavioral Research Advancements in Neuroscience (which cleverly shortens to BRAIN), which I found through a Google search of “neuroscience summer program” or something of the sort back in January. There are 36 of us, ranging from rising sophomores like me to recent graduates, and we’re all staying in Emory University’s dorms. During the day, though, we’re in various labs in Atlanta area--a lot of people are at Emory or Georgia State; I’m the only one at Georgia Tech this year. We’re also serving as subjects in an educational “experiment” to see if there’s another (possibly better) way of getting undergrads involved in research, so we were randomly split into LeftBRAIN and RightBRAIN groups. I’m in RightBRAIN, so I’m going the traditional route, joining an established lab’s on-going project, and I’ll do a research report and presentation at the end of the summer. LeftBRAIN people are all together during the day, learning different research techniques and by the end of the program, they’ll have a research proposal for a new experiment. I arrived on May 26th and had a quick intro meeting and campus tour the day
after. We also had entry interviews or focus group discussions to help the researchers understand our perspectives on science in general. We had the first weekend off in observance of Memorial Day, so a group of us decided to go explore the city. Then on Tuesday, we began orientation, a “crash course in neuroscience” to give everyone, especially those of us who don’t have much of a neuroscience background, a foundation to begin our research work.
I began working in my lab the following Monday. My lab is more on the psychology/cognition end of the neuroscience spectrum, looking at memory in older and younger adults. In particular, I’m working with Eric, a postdoc, on a new study in young adults. We’re using fMRI to see which parts of their brains are activated when they try to recognize words they’ve seen before. Two weeks in, I’ve finished the programming for the pilot experiment, and I’m also preparing to test older adults in a pilot for another study.
Payday! (AKA Halfway Mark) 06/30/2010
Just got half of my stipend today--and this marks the halfway point of the program. When we were all introducing ourselves on the first day, a lot of people, especially the older students, noted that this summer is helping them decide if research is a suitable career path for them.
Coming in, I was thinking about an MD/PhD program after college, so that I could combine clinical work with research. I did an internship at a drucom-
panydrug company before freshman year of college, and while I was there, the physician-scientists I worked with felt that having both degrees was really beneficial: a medical degree helps with working with patients, while a doctoral program hones the critical thinking skills crucial for research. But during these five weeks, I’ve already felt myself moving away from doing research as a major part of my career, and possibly toward public health. It’s not that I’m not enjoying myself; I really do like the work that I’m doing. Also, since I’m in a psych lab, I see subjects regularly (I ran my first one last week, and will have two tomorrow), so it’s not like I’m stuck in at a bench pipetting chemicals all day with minimal human contact. This may just be my naivete and lack of experience, but as I was discussing with one of my roommates, I feel like my skills are better suited for applying scientific information and regularly working with patients and their families as a physician, rather than actually going in and doing the research itself. And I don’t doubt that research helps people, but from all of my experiences so far, I find that having direct contact with the people I help is more gratifying. However, getting experience with designing and running studies is definitely worthwhile for any doctor, to help with understanding the vast amounts of literature out there. And I don’t view this summer as a make-or-break experience, because what I’m doing now is just one out of many types of research.
On a related note, last week, during our weekly “all BRAIN” meeting, we had a video conference with Dr. Thomas Carew. He’s the former president of the Society for Neuroscience, and he worked with Nobel Laureate Eric Kandel on aplysia, a large sea slug. Their work contributed a huge amount to what we now know about memory and learning. He was wonderfully down-toearth and very funny, and we had the opportunity to ask him questions, both about his papers we read during orientation and becoming a scientist. orientation, I read off a question my roommate wrote, asking him what the most important quality in an aspiring scientist is. His answer: unbridled curiosity, which fuels the passion and drive to go into the lab whenever necessary, even on Friday
nights and weekends, until the question is solved. “You’ve got to really want it,” in his words.
Off to go enjoy some of the dinner I helped prepare--we’ve fallen into a trend of having one person cook each Wednesday, and everyone who wants to come chips in to help cover the cost. So far we’ve had spaghetti and Japanese curry; tonight it’s jerk chicken!
A “Typical” Day 07/28/2010
As I’m nearing the end of the program, it’s amazing to think back to the beginning and all that I’ve accomplished this summer. As I mentioned in my first post, after our week-long orientation, we dove right into lab work. I came into my lab just as Eric, my daily mentor, was beginning to implement the experiment that I’m presenting in a week (eek!). My lab experience from this summer was very different from most of my friends’, since it’s a cognitive neuroscience lab. We don’t have a single test tube or Bunsen burner in sight (though we do have a syringe for the electrode gel used during EEG experiments). Nor do we have a dress code requiring closed toed shoes or pants; we just need to look nice for when subjects come in to do the experiments. During orientation, our instructors stressed the importance of keeping a lab notebook, but since we’re not doing complicated procedures where putting in too much of a chemical could mess up the results, I just have a regular spiral notebook to record anything I deem important or interesting, and issues that come up while experimenting (say, a participant falling asleep in the fMRI scanner--it has happened!) are record-
ed in binders, one for each study. Since we did an entire experiment in 8 or so weeks, with me working full-time, it’s also worth noting that my experience is fairly different from that of a student researcher working part-time in a lab over several years.For the most part, I worked standard hours, coming in a little after 9 and leaving around 5 or 5:30, with the majority of that time spent at a computer. Initially, I worked on programming the experiment, using a software program called E-Prime. It sets up the various screens of instructions and stimuli that a participant sees, and also takes care of recording their responses when they press keys. After some revisions, I began running subjects on the experiment (this summer, I also tested participants on a couple other studies that the lab is conducting). As I wrote earlier, it was difficult having people sign up via the usual method, so I ended up working around 2 extra hours every night, testing people from my program. During that time, I also wrote scripts that sorted the data into the different categories we need, using a programming language called Python. It’s a fairly easy language to pick up, but pretty frustrating when a tiny error messed the whole thing up! And now, I’m working on analyzing the data and on my poster and paper, which are due in exactly one week. It’ll be a lot of work, but very rewarding!
Closing thoughts 08/08/2010
I arrived home yesterday, and I find myself missing life back in Atlanta (minus the heat and humidity!). Working on memory research in humans this summer was even more
confirmation that neurobiology is what I should concentrate (major) in--I still find the brain immensely fascinating. But while I’d be open to joining a cognitive neuroscience lab back at school, I can’t see myself doing this type of work as a full-time job.
However, one of the other posters at the symposium caught my eye (it was actually my second choice on the list of possible labs we received before arriving): the girl who presented it did research on how psychotropics taken during pregnancy affect the babies. That kind of work is moving a little more towards public health, which I’ve mentioned that I’d like to explore more. Nevertheless, I wouldn’t have traded my lab placement, as I had the chance to work with really wonderful people and I did learn quite a bit. If you’re interested in this program, or a similar one, for next summer, start looking early! I did quite a bit of online searching, typing in phrases like “premed internship” and “neuroscience research program”. There’s also a massive list of programs by the pre-med advisors of another school (I think it may be Columbia). Also, a lot of deadlines are around late January to February. In general, I think that summer research programs like this one are the best for meeting people in your field of interest, outside of your home institution (after all, you do have a lot more time to make those connections during the school year). The established scientists I’ve encountered will be wonderful sources of advice, and I have no doubt that my friends in the program will go on to do great work in the future. So, that’s it! Thanks for reading, and good luck in the upcoming school year!
Heidelberg Castle (Near where our annual conference is
Essen, Germany Nan Du My name is Nan, and I’m a rising junior at Harvard University, concentrating in biomedical engineering (S.B) with a secondary in health policy. Originally, I’m from the awesome state of Rhode Island, so I’m a huge fan of coffee milk and I tend to understand most of the Family Guy jokes I like watching soccer (yay World Cup!), reading about interesting science news, and exploring new cultures! This summer, I’m going to be blogging for WISE from the “land of poets and thinkers” ,and delicious chocolate, sausage and beer. I’ve been given the amazing opportunity through a RISE internship, which is through the DAAD, to work in the Transfusion Institute at the Universitätsklinikum (University Hospital Essen) . My german is extremely lacking, and this is my first time working with stem cells(I’ll elaborate on my project later), so it’s sure to be an experience! So here’s to some interesting cultural interactions in a foreign lab environment!
PS. Quick explanation of title: Forschung means research in german. Du means you in german, and it is also my last name. I also did a bit of word play with it, so it could be thought as Do. So either Do Research, or my personal research, or you research! Haha, up to you! Sorry if that was lame!
On a research note, I’m finally getting started on my research project which has been kind of vague. Basically my first project is to isolate of human umbilical cord derived mesenchymal stromal cells and endothelial colony forming progenitor cells. In doing so I hope to test some new sera for MSC outgrowth, proliferation and cultivation, and characterize these MSc through differentiation assays and use
while it is still slightly disorganized, it has This schematic is much of what I’ll be definitely impressed me thus far. I have just come back from the grand conference which doing this summer. is held in Heidelberg for the other 300 RISERS who are located all around Germany. The people I met were extremely diverse, hailing from not only US, but also England and Canada. Their research ranged from biomedical engineering to aerospace, but one thing for sure- everyone enjoyed the German culture and researching. All had this passion to learn new things. Yeah, it sounds a bit corny, but picking up a conversation about their research was remarkably easy and most were eager to inquire about your Image Citation: Reinisch A., Strunk D. (2009). Isolation project as well. and Animal Serum Free Expansion of Human Umbilical Cord Derived Mesenchymal Stromal Cells (MSCs) and Endothelial Colony Forming Progenitor Cells (ECFCs).
The first step is learn about umbilical cords, and basically how to get cells from them. Luckily, over the weekend, we managed to get 10 umbilical cords which I was able to practice on, which meant cleaning them and trying cut out the vein. It’s like dissection class all over again, hopefully my hands will become more steady! It was much more difficult than I envisioned, but really rewarding!
Besides the awesome people, RISE provides you with a stipend for spending, health insurance, and a German Rail Pass for four trips( Two are meant for your journey to Heidelberg). It realizes that while many are serious about their research, we also want to explore Germany and Europe. As a result, there is this acceptance that most of the students will be traveling on the weekends. Furthermore, it puts you in contact with many industries and German universities, if you are interested in pursuing a Masters/ PhD in Germany.
RISE is definitely a relatively new summer program and has quite some improvements So now that you know a little of what to be made, but at the moment, it has defiI’m doing in lab, I should probably elabnitely provided the best combination of adorate a bit more about DAAD and RISE. venture and research that I was looking for. RISE, also known as Research in Science and Engineering, is the brain child COOKING? SCIENCE? of the DAAD (Deutscher Akademischer 07/23/2010 Austauschdienst EV/ German Academic Exchange Service) and the German It just hit me that we only have a little more Chemical Society. Science has become than one more month left in summer. What increasingly dependent on internation- this also means is that I’ve been in Germany al cooperation. While of course, there for more than 5 weeks now. Now, to be peris still some competition between lab fectly honest, I was downright terrified of groups in attempts to find the next cure this internship because of a few things (1) or biggest discovery. However, what I’m in a foreign country, (2) I don’t speak/ many are finding, and what RISE at- understand any German, and perhaps most tempts to advocate is the importance importantly (3) I lack basic cooking skills. intellectual exchange and partnership. So I know you must be wondering on why The program is in it’s 6th year and I’m talking about cooking, when this blog is 07/13/2010
suppose to be dedicated to my research internship. The thing is, my adventures with cooking have kind of paralleled my experiences in the lab. In the beginning, I was armed with the very basic toolscell culture( changing media, taking care of cells, sprouting assay, some histology knowledge, etc), and frying eggs/ramen. In other words, I could survive if you threw me in a foreign lab/ environment, and probably have very high cholesterol/toned arms at one point. However, to be just at that point, leaves your brain and stomach quite hungry for something else with a bit of spice. 5 weeks later, I’ve cut up human umbilical cords and raised over 50 well plates+ 40 flasks with varying media and cell types. I’ve taken over two incubators, figured out the FACS machine(used to sort different cell types- ie mesenchymal stem cells from human umbilical vascular endothelial cells), and overcome a language barrier. I won’t sugar coat anything, it’s been an interesting challenge to adapt to the new research topic. Previously, my knowledge of stem cells was quite limited, and I had no idea how to read a FACS graph(instead I focused on the pretty colors).
In the kitchen, I can finally crack an egg without having shell pieces in my skillet. My eggs aren’t too salty, and I’ve added vegetables into my diet. I’ve managed to cook tortellini, by using a skillet instead of a pot because I have no pot My last burn mark was in the first week, and to my great happiness, I have not burned a kitchen down. I’m no where close to calling myself a cook, but my meals atleast have some more variation in them now.
Another interesting parallel, is this discussion I had with my graduate student about cooking. He said, that if you can do research, you should be able to cook. It has the same basic things- various of variables, a general hypothesis/ envisioned meal in mind, and lots of patience. Patience is key to everything in cooking, from waiting for the pasta to boil to taking the time to allow the flavor of each ingredient to seep into the food. Many times, when we are tired and grumpy, we throw in that ramen package because we need food. Yet, when we eat it, it isn’t as good or as yummy as if we had cut up some fresh ingredients and stirfried it ourselves.
The same is seen in the lab. We can cut corners sometimes, such as maybe not looking as closely at the flasks for cell growth or decreasing the incubation time because we need to get home. It still gets us results, but perhaps not the most ideal. However, cooking and science are also both amazing in that sometimes if you try something new, you might get one epic meal.
UNDER THE SCOPE 07/28/2010
After around 6 weeks of running around, I’ve finally settled down into a somewhat routine schedule.
8:30- 9:00- I arrive which is in the Robert Koch’s Institute on the second floor, and proceed to speak to my graduate student- Stefan regarding the day’s plans and any important issues/ updates that I should be aware of. For instance, if there was any contamination in the incubator; if so, I would need to check all my plates for security reasons. The discussions tend to differ depending on the day, and are one method of checking in. I also get informed about lab gossip- such as Sorian(another graduate student from Berlin) becoming a father in February.
9-12:00: I’m mostly in the Cell Culture room, dominating the left bench with German radio blasting in the far corner. Like I’ve said in previous posts, I have a relatively uncomplicated project of testing out new serum for the lab and characterizing cells from the umbilical cords that I am given from the hospital. Usually on Mondays and Thursdays, I go through my 50-60 well plates of MSCs and then my 40 T75/T175 flasks of HUVECS by a confocal microscope. While doing so, I make careful notes regarding the morphology, proliferation and also look for cases of possible mixing of MSCs and HUVECS. The reason that I need to look out for mixing is because these are primary culture. Thus it is possible that MSCs can grow in HUVEC culture, but since I’m freezing many of these cells, it is imperative that we understand what cell types they are. The results of my data will probably determine the lab’s future serum use, so it is important for me to take detailed notations regarding cell differentiation and monitor possible splitting opportunities. It is interesting to see how my
past research on Notch cell signaling factors in as a reason why splitting is necessary as if the cells begin to grow over one another (even in just one patch), may send signals to stop growing.
A few weeks ago, this schedule was a bit different as I was actually cutting up umbilical cords. My graduate student would stop at the newborn area in the hospital and see if I had any fresh newborn umbilical cords. They would be stored in a PBS+BSA solution, which would keep it relatively fresh and cells happy until I received them. The degree of redness of blood also is used to indicate freshness of the blood. I felt like a vampire sometimes when I would often have to discard umbilical cords if they were not fresh enough… Most of the morning would then be spent decked out in gloves and lab coat, cleansing the umbilical cord of all the blood through some extreme washing. Depending on the length and thickness of the cord, I would then determine the number of pieces of cord to put in each well of a 6 well plate. The next part is perhaps the most fun- you rip all the extra gelatin like structure away from arteries and veins. Most times you are lucky to get one artery and one vein from the cord, but to my graduate student’s delight, I managed to discover a technique to isolate both. I accredit this to old knitting and friendship-bracelet making skills. Once you cut these veins and arteries up, they must be placed in a 6 well plate and careful to expose them to as much surface area as possible . Fun fact- Katy Perry’s California Girls will have played atleast 6 times on the German radio by the time I go to lunch. So I’m kind of sick of that song…
12-12:45- Lunch at the Mensa- hospital cafeteria. This is also where we have our daily german food lesson.
1-6:FACS/Flow Cytometry analysis( a method to purify the cells, and also technique for counting and examining more closely microscopic particles). There is more media changing with also the possibility of a few seminars from visiting professors regarding stem cells and new technology. If there is any free time, I’ll probably scan some stem cell literature or update my lab notebook. If cell culture is not completed in the morning or there is a reservation of the TC hood, cell culture will be continued in the afternoon.
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