[ Editorial Board ] Robert Aboukhalil Maria Nattestad
Editor-in-Chief Managing Editor
[ Executive Board ] Dr. Charla Lambert
Program Manager, Science & Training Cold Spring Harbor Laboratory Meetings & Courses
Dr. Alexander Gann
Dean and Professor Watson School of Biological Sciences
Dr. David Stewart
Executive Director Cold Spring Harbor Laboratory Meetings & Courses
[ Contributors ] Jaclyn Novatt Cristina Aguirre-Chen Michael Giangrasso Emilis Bruzas Devinn Lambert Arkarup Bandyopadhyay Elizabeth Hutton
[ Images ] • Johannes Jansson, Wikimedia • George Joch, Argonne National Laboratory • The Associated Press • Manchester Digital Laboratory • David Benbennick, Wikimedia • Wired Science • Kris Krüg, Flickr
CONTENTS Editorial: Rethinking STEM education STEM literacy for all careers
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Why every child should learn to code 6 Biobus: Science on the move
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Hands-on science at the DNA Learning Center 9 The coral reef corner
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The exoneration of James Bain
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Maryland v. King: Is DNA private property? 13 Topology and bacterial replication
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Spatial representation in neuronal populations 16 Q&A with Dr. Siddartha Mukherjee
Current Exchange is a student-run magazine, published biannually as a joint venture between the Meetings & Courses program and the Watson School of Biological Sciences at Cold Spring Harbor Laboratory.
Current Exchange is published by 11factorial. For more information, visit our website at 11factorial.com or contact us at hello@11factorial.com. The opinions expressed in the articles herein only reflect the opinions of their respective authors. All articles here are licensed under the Creative Commons BY 2.0 License.
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EDITOR’S DESK
Rethinking STEM education Robert Aboukhalil / PhD Student, Watson School of Biological Sciences, CSHL
Whenever science, technology, engineering, and mathematics (STEM) education is brought to our attention, it is often to warn us of a pending shortage of STEM graduates. In 2012, the President’s Council of Advisors on Science and Technology released a report urging the U.S. to produce 1 million more STEM graduates, just to keep up with economic growth. While having more scientists and engineers may be beneficial for the economy, we also desperately need a scientifically literate populace, given that STEM graduates shy away from political roles. In fact, out of the 541 politicians who currently serve in the U.S. Congress, we only find 1 microbiologist, 2 physicists, and 6 engineers1. In that regard, we tend to overlook important aspects of STEM education: (1) STEM literacy for all regardless of career path; (2) computer programming skills for children starting at a young age; and (3) STEM literacy for all, regardless of socioeconomic background. We begin this issue by discussing the benefits of moving the focus away from careers in STEM, and onto STEM literacy for everyone. On page 4, Jaclyn Novatt explores the reasons why even kids not interested in STEM careers need to be scientifically literate. As recent events suggest, we would do well to heed her advice. One notable example is the return of diseases that were previously eradicated in the U.S., largely due to the
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Out of the 541 politicians who currently serve in the U.S. Congress, we only find 1 microbiologist, 2 physicists, and 6 engineers.
anti-vaccination movement. For instance, measles, which infected millions of children in the 1950’s, was successfully eradicated in the early 2000’s, with only 37 cases in 20042. But more recently, in 2014, the CDC reported a record 610 cases of measles in the U.S., largely due to outbreaks in communities where many were unvaccinated3. Furthermore, as climate change increasingly becomes a problem that cannot be ignored, it is only when the citizenry is informed and insists on change that politicians will start taking this issue seriously. On page 6, Maria Nattestad argues that all children should learn to code, both to improve their career prospects, as well as to empower them to take initiative. However, we must be cautious when introducing computer science in the education system. As she warns, we must not let a rigid curriculum and grading overshadow learning: “we must remember to let students challenge themselves, experiment, fail, fail some more, and then succeed, without penalizing them with bad grades”. Next, we feature the BioBus, an innovative approach to teaching kids about science aboard a renovated 1970’s transit bus. As discussed by Cristina Aguirre-Chen on page 8, the BioBus “visits 100 New York City area schools, logs in 145 teaching days, and reaches over 20,000 K-12 students.” Since
all the microscopes are on the bus, this allows them to reach children from all socioeconomic backgrounds in New York City. Finally, on page 9, Maria Nattestad presents a profile of the DNA Learning Center, and highlights several of their pioneering education efforts, both in the classroom and online. This includes the popular 3D Brain app, which has so far been downloaded over 2.5 million times and was even featured in an Apple ad during the 2013 Academy Awards. In addition to STEM education, this issue features articles ranging from DNA privacy and forensics, to the discovery of grid cells and place cells, which won the 2014 Nobel Prize in Physiology and Medicine. In this issue’s Coral Reef Corner, we discuss the history behind the coral reef hobby community, and on page 14, we explore how topology and the Möbius Strip play an important role in biological systems. We end with a Q&A with Siddartha Mukherjee, author of The Emperor of all Maladies: A Biography of Cancer ■ References 1. JE Manning. Congressional Research Service, http://1.usa.gov/1xditpE 2. B Berkowitz and A Cuadra, Centers for Disease Control and Prevention & The Washington Post, http://wapo.st/1lJLUjW 3. Center for Disease Control and Prevention, http://1.usa.gov/1hR3aN8
FEATURED
STEM literacy for all careers Jaclyn Novatt / Postdoctoral Fellow, CSHL
STEM. Science, technology, engineering, and mathematics. Originally introduced in the early 2000’s by the National Science Foundation, this acronym became a buzzword in education ever since President Obama’s 2009 “Educate to Innovate” call to action1. Since then, the US Department of Education began a STEM education initiative to add 100,000 new STEM teachers and to increase the number of college students who graduate with STEM majors by 1 million in the next decade2. The main purpose of the government’s initiative is to encourage more students to pursue STEM-related careers. Eric Spiegel and David D. Etzwiler from Siemens have predicted that if the U.S. does not increase STEM training, “research and innovation will take place in other countries, squandering any potential of advanced manufacturing
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I believe the more important point is that everyone, no matter what path in life they take, needs STEM literacy to function in today’s society.
in the U.S.”3 The effects of this initiative can be seen locally in many ways: (1) there are programs at Hofstra University4 and Stony Brook University5 to educate STEM majors and future STEM teachers; (2) Sesame Street is doing a big push for STEM content (kids are watching Super Grover 2.0 using levers and pulleys to help characters solve problems); and (3) I recently responded to a request from my children’s daycare for help in designing a “little scientists” program for the 2, 3, and 4 year olds. Recently, I participated at a Girl Scout Imagine the Possibilities conference, designed to expose 7th, 8th and 9th grade girls to STEM careers. In addition to isolating DNA from their cheek cells with me, they participated in hands-on workshops in computer science, zoology, chemistry and mathematics. The conference also encouraged the girls to interact with women in various STEM-related careers, and the keynote speaker was Marissa Shorenstein, president of AT&T’s New York office, who encouraged the girls to pursue STEM majors and careers.
I had a great time at the conference, and I enjoyed working with 25 very enthusiastic girls. However, I left the conference with an uneasy feeling. While I applaud this effort and truly believe that STEM education is important at all levels, I am worried that by focusing so much on STEM careers, the unintended message is: “if you’re not interested in being an engineer, computer scientist, or other STEM professional, then you don’t matter and don’t have to pay attention”. I believe the more important point is that everyone, no matter what path in life they take, needs STEM literacy to function in today’s society. I have seen how difficult and scary life can be without a basic knowledge of STEM. While I was in the hospital during a high-risk pregnancy, one of my roommates was told by her doctor that her cervix was short and that she was put on bed rest to prevent premature labor. Once the doctor left, my roommate turned to me and asked “Jackie, what’s a cervix?” My heart broke for her as I explained. I know how scared I was with my pregnancy complications, and I could only imagine how
much more terrifying it would have been had I not been able to understand what my doctors were telling me about what was happening inside my own body. A few years ago, I taught a basic Human Biology course at a local college. My students were not science majors, so my goal for the class was to make my students more informed patients—if their doctor said their cholesterol or blood pressure was high, I wanted them to know what it meant. This turned out to be a great approach, as most of my students entered the class with little to no knowledge of how their body worked. For example, some of my female students didn’t understand what their menstrual cycle was, and none of them knew what a blood pressure of 120/80 meant. The importance of STEM in everyday life goes beyond health-related issues. My chemistry students are amazed when I do mental math and estimate whether an answer should be approximately 0.01 or 1 million. This ability to quickly perform mental calculations is essential in every day life— whether you’re figuring out if it’s cheaper to buy paper towels on Amazon or at the grocery store, or if the bin you see at the store is actually large enough to hold all of your children’s toys.
So, while I believe the push for STEM education is extremely important, I believe the focus on STEM careers is misplaced. This focus unintentionally alienates those students who are interested in music, history, economics, or politics, leading them to incorrectly believe that STEM is not important if they choose to pursue a non-STEM career or if they choose to leave the workforce and focus on raising a family. STEM literacy is important for everyone. If you are interested in business or finance, you need a solid background in math and statistics. If you are interested in sports, you need to know how your bones and muscles work and how your body obtains energy both aerobically and anaerobically. A lawyer needs to understand the biology behind DNA evidence, the physics involved in car crashes, and even entomology as used to determine the age of remains in order to properly question expert witnesses. For students interested in politics, an understanding of STEM should be crucial. If Governors Cuomo and Christie had even a basic knowledge of virology and epidemiology, they might have handled the Ebola situation quite differently. If our government leaders had a basic understanding of geology and climate science, perhaps the climate change debate would no longer be a debate. I believe former congressman Todd Akin’s infamous words speak
for themselves about his knowledge of human biology when he said “If it’s a legitimate rape, the female body has ways to try to shut that whole thing down.”6 Most importantly, anyone who needs to visit the doctor should have a basic understanding of how their body works. How many Americans who are on statins to regulate cholesterol know what exactly cholesterol is? I feel we as a society would take much better care of ourselves and our children if we had a better understanding of how our bodies worked. In short, I truly applaud the push for STEM education but would encourage teachers and workshop leaders to emphasize the importance of STEM education for all, not just those who choose to pursue STEM careers ■ References 1. The White House Office of the Press Secretary, http://1.usa.gov/1K5aO78 2. U.S. Dept. of Education, http://1.usa. gov/1eTep6F. 3. Peter Sacks, The Fiscal Times, 2014, http://bit. ly/1wHjhCP. 4. Hofstra University, 2014, http://bit.ly/1ycYVIu 5. Stony Brook University, 2014, http://bit. ly/1xbguHn 6. Chris Gentilviso, Huffington Post, 2014, http:// huff.to/1ctWUbC
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FEATURED
Why every child should learn to code Maria Nattestad / PhD Student, Watson School of Biological Sciences, CSHL
There are few things more empowering to a young person than building her own mobile app. The benefits extend far beyond profit or an impressive addition to a college application, and include lasting self-confidence and grit. Coding enables you to take your ideas and turn them into reality while learning problem-solving and logical thinking. You have to break problems up into a series of manageable steps that are very clear and logical to make the computer do what you want. These skills are important in many of the careers we most want to encourage young people to
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enter, such as science, engineering, and entrepreneurship. Computer science is one of the most lucrative and highest-paid college degrees, and while women represent 57% of college graduates across all fields, they account for only 18% of computer science graduates according to the National Science Foundation. Nonprofit organizations are trying to address these disparities and increase overall engagement with computer science for young people.
Code.org One such organization is Code.org, which started the Hour of Code movement to incite people of all ages to try computer science. Just over the last two years, they
Computer science is a great subject to teach in school, but when we do, we must remember to let students challenge themselves, experiment, fail, fail some more, and then succeed, without penalizing them with bad grades
have reached more than 90 million children and adults across the world. The Hour of Code presents a great chance to start the conversation about teaching computer science more broadly, making it available in every high school so that it is taught earlier. Considering the analytical and creative problem-solving skills involved in coding, it could be very beneficial to make computer science a standard part of the curriculum, right alongside English, social studies, math, and science. During Computer Science Education Week last December, I organized an Hour of Code event at Cold Spring Harbor Laboratory, attended by just over 100 children and adults. The biggest lesson I learned from organizing the Hour of Code was to give children a way to learn coding that let them experiment and make whatever their hearts desire. The best resources I found were Scratch (scratch.mit. edu) and Khan Academy because these gave the kids freedom to explore.
Girls Who Code While we wait for school boards and state legislatures to catch up, others are trying to expand computer science teaching through programs outside of school. For instance, Girls Who Code is an organization dedicated to addressing the gender gap in technology, which they do by holding a summer camp for high school girls and supporting local after-
7 school clubs across the country. The curriculum consists of one project per month that is completed by teams of girls, and is designed not only to teach computer science but also teamwork, creativity, and problem solving.
so that students’ learning can be assessed by standardized tests. If we introduce computer science in the classroom, we must make sure the curriculum does not get in the way of learning.
I and about 200 other instructors are involved with Girls Who Code to teach young women computer science and it has been a very rewarding experience. Initially, I found it to be a rocky road because the students are accustomed to being told exactly what to do at every step that they are reluctant to experiment and teach themselves. By introducing them to project-based and selfdirected learning, I hope to inspire them to take initiative and become an active part of their own education. Based on my experience with the club, I concluded that the most important thing we can teach children is to take initiative, teach them to teach themselves, and have the grit to stick with it and pursue difficult challenges.
Furthermore, due to grade pressures, it is easy for kids to dismiss difficult projects they would learn a lot from, in favor of easier projects. Computer science is a great subject to teach in school, but when we do, we must remember to let students challenge themselves, experiment, fail, fail some more, and then succeed, without penalizing them with bad grades.
Computer science in the classroom Subjects in a traditional classroom are taught in a certain order, and teachers are required to cover a specific list of subjects
By making Girls Who Code an after-school club, we avoid these issues, which enables us to give them a space where they can learn without the fear of failure.
Final thoughts Computer science allows students to experiment, solve problems, and express their creativity, which I would argue most subjects in school are not easily adapted to do. In computer science, children can work together to make a larger project like a video game,
which makes it a great vehicle for teaching crucial soft skills like teamwork and leadership. I agree with Code.org that we should bring computer science into all schools at all ages, but I also worry that by teaching it in a traditional way, we will miss out on the most important thing kids can learn from the experience: that (almost) anything is possible as long as they take initiative and teach themselves. Computer science should be for everyone, and organizations like Girls Who Code and Code.org’s Hour of Code are a great step in the right direction. Computer science education could hold the key to many of the things we want for people in our society: better jobs, pathways out of poverty, and more scientists ready to tackle the challenges and opportunities in the upcoming era of data â–
The Biobus: Science on the move Cristina Aguirre-Chen / PhD Student, Watson School of Biological Sciences, CSHL BioBus was created in 2008 by Cell Motion Laboratories and is known as a “high-tech laboratory on wheels.” This former 1974 transit bus is equipped with $100,000 worth of state-of-theart microscopes, and its staff, who are primarily Ph.D.-level scientists, travel almost daily to elementary, middle and high schools in the New York City area with the aim of inspiring the next generation of young scientists. While on the bus, K-12 students have the opportunity to use a phase-contrast video microscope, a fluorescence microscope, and a scanning electron microscope—instruments normally used only in high-end research laboratories—to visualize everything from a live beating heart of Daphnia, a miniature aquatic animal commonly known as the water flea, to green-glowing cellular organelles. Over the past seven years, the New York City metropolitan area has experienced a transformation in the way science is introduced and taught to K-12 students. Through BioBus, students are able to actively participate in the scientific discovery process
by conducting hands-on experiments with real-life scientists rather than learning scientific concepts solely through traditional textbook-based learning. This concept has reaped many rewards, with even the most skeptical of students either now interested in science in general or, better yet, as a potential career. The sense of wonder and curiosity for science that Dr. Ben Dubin-Thaler, founder of Cell Motion Laboratories, and his BioBus staff have ignited through their immersive and collaborative science programs is quantifiable. Notably, a survey of 586 students from fifteen low-income schools found that just one hour aboard the BioBus changed students perspectives on science in profoundly positive way. After participating in a single BioBus laboratory module, the majority of students surveyed felt that science was fun, that scientists were people they could relate to, and that they could see themselves as a scientist. As a testament to its ability to instill excitement for science among K-12 students, BioBus has rapidly grown in popularity among teachers, schools, and community leaders and has proven to be an important driver of science education. In fact, during the course of one school year, BioBus visits 100 New York City area schools, logs in 145 teaching days, and reaches over 20,000 K-12 students.
One of the primary objectives of BioBus is to ensure that all students, from any culture or background, have the opportunity to engage in scientific discovery. To this end, BioBus devotes greater than 60% of its time to serving high-poverty communities, which traditionally have not had access to these types of scientific resources. Through generous funding from companies, such as the life science companies Regeneron and Life Technologies, foundations, and individuals, BioBus has been able to not only sustain its operations, but also to expand its science education program. In 2013, BioBase, the brick-and-mortar science center located in the newly-built Lower East Side Girl’s Club in Manhattan, was constructed. In keeping with this stateof-the-art community center, the BioBase facility includes an 800-square-foot microscopy center, a 40-person multimedia amphitheater, and a 4000-square-foot living green roof. Here, students are able to participate in school-day field trips, which cover topics that are aligned with New York State Common Core Learning Standards (CCLS), as well as weekend events and summer camp programs. In addition, BioBase offers free, after-school programs that are open exclusively to girls and young women so that they may engage in science discovery and learning in a inviting and supportive setting ■
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Hands-on science at the DNA Learning Center Maria Nattestad / PhD Student, Watson School of Biological Sciences, CSHL The DNA Learning Center (DNALC) first started to take shape in 1985 when Executive Director David Micklos held teacher training workshops on the latest recombinant DNA technologies. The following year, he and his colleagues drove their first Vector Van across the country to disseminate their innovative ideas about handson science education. Now, 30 years later, the DNALC is a global leader in molecular biology education with a wide array of innovative education initiatives. As the first science center devoted exclusively to genetics education, the DNALC has developed a strategy for outreach that revolves around lab field trips, mobile laboratories, summer camps, and teacher training. Every year, the DNALC hosts lab field trips for 20,000 middle-school and high-school students who perform hands-on laboratory experiments such as DNA extraction, restriction enzyme analysis, forensic DNA analysis, and introductory bioinformatics analysis. DNALC instructors also travel to regional schools, bringing the experiments to another 10,000 students each year. Over the last 26 years, the DNALC has taught nearly half a million student labs, and provided training for over 33,000 educators through workshops held worldwide. The Dolan DNA Learning Center, in Cold Spring Harbor, contains four state-of-theart teaching labs, a bioinformatics lab, and a museum about the history of molecular
biology, inheritance, and human evolution— while DNALC West, in New Hyde Park, and Harlem DNA Lab, in New York City, each have one teaching lab. As expressed by Bruce Nash, Assistant Director of Science at the DNALC, the larger mission of the DNALC is to “let students glimpse the world of modern biology.” Through their various efforts, they “train teachers, teach students, and provide approachable tools for biochemical and bioinformatic analysis—democratizing ‘big science’ for the world.”
In the mid 1980’s, David Micklos and colleagues filled DNA Vector Vans with pipettes and centrifuges, traversing the country and holding weeklong teacher training workshops along the way.
To extend its reach far beyond Long Island, the DNALC has developed a great collection of online educational tools that can be used by students, educators, and the public. Receiving over 6 million visitors a year, this award-winning suite of over twenty educational sites provide instruction about genetic disorders, the molecular basis of cancer and cognition, eugenics, and the history and current state of molecular biology. Entering the era of high throughput sequencing and genomics, the DNALC has led efforts to bring students in touch with new bioinformatics methods, first through Sequence Server and more recently via DNA Subway,
The DNALC’s 3D brain app was featured in an iPad ad during the 2013 Academy Awards. The app has been downloaded over 2.5 million times and is rated as a top education app on iTunes.
an online system for viewing and analyzing DNA sequence from a number of experimental approaches. For instance, the Blue Line of the DNA Subway allows students to perform quality control and analysis of short sequences, identify and compare related sequences, and construct phylogenetic trees, while the Green Line allows students to perform basic transcriptome analysis. In short, the DNA Learning Center has impacted biology teaching and learning regionally through local programs and globally through its affiliated programs, educator workshops, and online educational tools ■
CORAL REEF CORNER
A short history of reef tank hobbyists Michael Giangrasso / PhD Student, Watson School of Biological Sciences, CSHL Michael has kept reef tanks since he was thirteen years old. In this issue of The Coral Reef Corner, he discusses the challenges and small victories encountered by hobbyists in their endeavors to sustain and propagate coral reef organisms in home aquariums.
The first successful tropical freshwater aquariums were kept in the 1950’s. Undergravel filtration, which effectively moved waste from the aquarium into a compartment at its floor, permitted rapid expansion of the fishkeeping hobby, which had until then been restricted to experts and scientists. Relying on a submersible heater to maintain water temperature, a filter for water quality, and compressor-driven air stones for oxygenation, these early tropical freshwater aquaria came to house an ever-expanding list of ornamental fish. While a handful of advanced enthusiasts experimented successfully with closed saltwater ecosystems during this time, the saltwater aquarium hobby did not gain popular traction until the 1980s. Due to advances in analytical chemistry, it became possible to decipher the composition of natural seawater. With the advent of artificial salt
mixes, saltwater enthusiasts were no longer reliant upon the ocean to ensure that a proper mix of trace elements and other compounds would be found in their home aquaria. Early saltwater tanks were stocked primarily with fish and decorated with bleached coral skeletons. While some success was initially reported with hardy varieties of coral and anemone during these early days of the hobby, further technological advancement would prove necessary for widespread experimentation with the coral reef aquarium. Due to the presence of symbiotic photosynthetic dinoflagellates within the tissue of many species of coral, highintensity light is required over the reef aquarium in order to encourage photosynthesis in these Zooxanthellae. In the 1990’s, high-output fluorescent and metal halide lamps became widely commercially available for the home aquarium. This technological advance, coupled with the introduction of the protein skimmer for waste removal, allowed for the reefkeeping hobby to engage an unprecedented audience. I was born in 1991, and by the turn of the century I was already involved in the tropical freshwater and goldfish sides of the aquarium hobby. I was a voracious young reader, devouring any and all fishkeeping literature I came across online and at the library. I would often imagine what it would be like to own a
reef aquarium, and drew crayon-colored pictures of my planned future tank that were inspired by the pictures I had seen in various books. When I finally saved up enough to afford a reef of my own a full 10 years ago, in 2004, it was confined to a tiny 15 gallon glass aquarium. I opted to light the small system using a metal halide fixture whose ballast weighed as much as a small child and whose surface, upon contact with the skin, was capable of delivering thirddegree burns. Everything about the tiny system was over-the-top, from the equipment deployed to the time employed in maintaining it. By the end of its four-year reign, it had housed a tremendous variety of life, including an eel, a giant sea anemone that took up half of the tank, a breeding pair of clownfish, innumerable species of coral and clam packed densely upon the rockwork and sand bed, and a whole host of strange invertebrate life. Today, a lot has changed in the reefkeeping hobby. Yesterday’s high-energy, higher-heat halides have now been replaced by inexpensive, intense LED lighting systems. These systems are highly programmable and represent the next leap forward in reef aquarium technology. In addition, water purification techniques have advanced dramatically. While my first reef was cutting edge with a venturi skimmer and a closed-loop circulation system, my current aquarium’s water passes through a sump, an external filtration unit contain-
ing an advanced needle-wheel skimmer, a refugium, chemically absorptive activated resins, and a randomly-cycling wavemaker to ensure optimal circulation. Many species which previously I had been taught were impossible to maintain in captivity when I was younger are now considered easy to keep. Additionally, as scientists and hobbyist alike learn more about the wild and captive reef ecosystems, aquarium husbandry techniques and practices are advancing in step. It was long thought, for example, that corals’
nutrition was almost exclusively obtained via the photosynthesis of their symbiotic dinoflagellates. Now, it is known that zooplankton and organic particulate matter (‘marine snow’) comprises a significant portion of the diet of most if not all cnidarians available to the hobby. Another major change that the hobby has seen and will see in recent and coming years is a shift in the availability of wild caught and aquacultured marine
organisms. Due to climate change and the wholesale exploitation of our world’s oceans and reefs, many species (including ‘staple’ species common to the hobby) are gaining a place on the IUCN’s list of endangered organisms. While only a small fraction of the fish and corals commonly kept in home aquaria are available from the aquaculture and mariculture industry, it is a small fraction that grows every month. Many species of clownfish, goby, and dottyback have been bred and even selectively bred in captivity, while most coral species are amenable to ‘fragging,’ a process during which ‘cuttings’ of coral are propagated and distributed to like-minded hobbyists. Regardless of where the hobby is going, it is fascinating to reflect on where it originated and the path it has taken to arrive at today’s level of success in keeping marine reef aquaria in captivity. The coming years will bring more knowledge and success with innumerable organisms both known and unknown, and will likely see the rise of sustainable methods of harvest for the aquarium trade as well as improvement and expansion of the repertoire of aquacultured species. I have enjoyed my past decade in the hobby immensely, and will surely enjoy the decades to come. If you have some spare change, free time, and a love for marine life, now is a better time than ever to become a reefer ■
DNA FORENSICS
The exoneration of James Bain Emilis Bruzas / PhD Student, Watson School of Biological Sciences, CSHL
In 1974, James Bain, a resident of Lake Wales, Florida, was convicted of rape, kidnapping and burglary and sentenced to life in prison at the age of 18. However, DNA testing carried out 35 years from the time of conviction proved Bain’s innocence and led to his exoneration in 2009, making him the longest serving DNA evidence-based exoneree. On March 4, 1974, a nine-year-old boy was woken up from his sleep by a man who then kidnapped the boy from his room, dragged him to a baseball field and raped him. The boy told the police the attacker was around 18 years old, had sideburns and a moustache and told the boy his name was “Jim” or “Jimmy”. The victim’s uncle thought the description of the attacker fit James Bain, then a student at a high school where the victim’s uncle was a vice principal. This led to the uncle providing the police with a photo of Bain. When presented with six photos of suspects, the boy pointed out Bain, even though only two of the suspects had sideburns. On March 5, 1974, the police questioned Bain at his home. Bain told the police he was watching TV at home during the time of the attack. Despite his alibi being supported by his sister, Bain was arrested.
Semen samples found on the victim’s underwear were sent to the FBI for blood type analysis along with a sample of Bain’s blood, because DNA testing was unavailable at the time. During trial, an FBI expert testified that the semen found on the underwear was group B, whereas Bain’s blood group was AB, as shown by the defense. However, the FBI expert stated that Bain had a “weak A” component in his blood and therefore could not be excluded from having deposited the semen. Despite weak criminological evidence and a supported alibi, Bain was convicted of rape, kidnapping, and burglary. The judge sentenced Bain to life in prison. The prosecution’s case rested largely of the victim having identified Bain in a photo lineup. In 2001 Florida passed a law allowing convicted prisoners to request their case being reopened for DNA testing. Bain presented four hand-written motions, requesting DNA testing of the criminological evidence from his case. All were turned down by the court due to post-conviction time limits for appeal imposed by the same law. However, after the limit was lifted by a law correction, Bain’s fifth request to appeal the court’s decision in 2006 was satisfied, which allowed Bain to secure DNA testing in 2009 with the help of the Innocence Project. The semen DNA sample did not match Bain’s DNA and he was therefore excluded from being the attacker. Later that year he was
declared innocent and released, overturning a wrongful conviction caused by eyewitness misidentification and improper forensic science. Bain received a compensation of approximately $1.7m from the state of Florida and received reintegration support from the Innocence Project. However, the real attacker has not been found to date. DNA testing using a variety of assays has changed the landscape of forensic science in terms of confirming identity, implicating the guilty and exonerating the innocent since the introduction of DNA fingerprinting in 1985. However, exoneration, which is the main mission of the Innocence Project, has been proven to be a very slow process. Only 321 people in 38 states of the U.S. have been exonerated through post-conviction DNA testing since 1989. This number is very small considering the incarceration rate in the U.S. (1% of total population, approximately 3 million people) and the estimates of wrongfully convicted people (2.3-5%, estimates of the Innocence Project). Causes for low rates of exoneration include high costs of DNA testing and staffing, lack or insufficiency of evidence (useful DNA evidence is left behind in only 5-10% of all crimes), difficulty of interpreting DNA mixtures, inefficiency of the criminal justice system, false claims of innocence by prisoners and others. Exoneration rates are expected to rise with increased funding and development of more sensitive and efficient DNA testing techniques ■
DNA PRIVACY
Maryland v. King: Is DNA private property? Devinn Lambert / PhD Student, Watson School of Biological Sciences, CSHL
The controlled, yet random process that creates a genome makes each of us unique, much like our fingerprints. However, unlike fingerprints, our DNA is not immediately apparent, and in this regard, is like a person’s private property. If DNA is someone’s property, then in the United States, it is afforded some protection by the Fourth Amendment of the Constitution, which protects a person against unreasonable searches and seizures of their property.
In all fifty states of the U.S., it is legal and required to collect DNA from convicted felons. In Maryland and 27 other states, it is also legal to collect DNA from people like King who have been arrested but not convicted of a felony. However, King’s DNA was used in litigation for a different crime (rape) than what it was originally collected for (assault). The central question in this case is whether a person’s DNA can be used to identify someone in the same way in which a fingerprint or photograph is used when someone is arrested. In February of 2013, this case was argued in front of the Supreme Court of the United States.
In April of 2009, Alonzo Jay King Jr. was arrested on charges of first- and seconddegree assault in Maryland. In addition to routine procedures such as fingerprinting, booking personnel swabbed the inside of King’s cheek to collect a DNA sample, which was in accordance with the Maryland DNA Collection Act.
In a 5-4 vote, the Supreme Court found that DNA is like a fingerprint, and in this framework there are no barriers for the police to collect and sequence the DNA of a citizen if they are accused of a serious crime. While in King’s case the sequencing of his DNA allowed for the coincidental connection to a previous crime was a benefit to the public, does collecting a private citizen’s DNA for one purpose and using this information for another purpose constitute excessive seizure?
The DNA sample taken for the assault charges linked King to an unsolved 2003 rape case, also in Maryland. When King was brought to trial for the rape, the defense argued that the DNA evidence should be ignored because its use would violate the Fourth Amendment and was therefore unconstitutional.
King v. Maryland sets the precedent that DNA is an identification tool that can only be used on people who are accused of serious crimes. If the restrictions on DNA sequencing are relaxed, the average person should feel as comfortable with giving their DNA sequence as they would their fingerprint.
On one hand, I support the decision because forensic DNA sequencing is often used just as the police would use a fingerprint. However, this decision concerns me because fingerprint identification is also used outside the criminal justice system. According to this legal framework, a person should be prepared to switch their fingerprints with a check swab to fulfill a job application or visa requirement. As sequencing technologies become more affordable, could a company justify a Gattaca-like policy of sequencing its employees’ DNA for identification purposes? Or, could the police sequence a suspect’s DNA before enough evidence was collected to formally arrest the person? From a public policy standpoint, I believe it would have been preferable if the Supreme Court found that DNA was not an identifier but instead private property, which has greater protections for searching, and clearer restrictions for how the property can be used Currently, there are many slippery slope possibilities for how DNA can be used and ethical questions that need answering. Most importantly, the legislative branch needs to follow up on the judicial branch’s actions to limit the use of DNA sequencing to only forensics ■
BIOLOGY + MATH
How topology almost made bacterial replication impossible Arkarup Bandyopadhyay / PhD Student, Watson School of Biological Sciences, CSHL Some years ago, in a microbial genetics lecture, I learned that when a double-stranded bacterial chromosome replicates during cell division, the two daughter chromosomes do not simply separate but remain interlocked with each other (Figure 1). These daughter chromosomes can slide, roll on their sides, but no matter what, they can’t untangle themselves. Technically, these linked daughter chromosomes are called catenanes. I remember wondering: why do the two DNA pieces remain linked together? The professor had told us that this peculiarity arises because bacterial chromosomes are circular in shape. I couldn’t wrap my head around this explanation for a long time and it is easy to see why with this toy experiment. If you take a strip of paper that can be glued together to make a closed, circular piece (Figure 2), it looks W C
W C
Figure 2: A closed, circular strip of paper
Figure 1: Electron micrographs of two interlinked DNA molecules (catenanes).
like a strip or a cylinder depending upon how wide it is. Now take a scissor (imagination may suffice if you are lazy) and cut through the middle along its length (dashed line). It easily separates out into two individual rings. So ‘circularity’ alone cannot explain this phenomenon. So what is really special about the circular DNA of a bacterium that prevents the separation of the daughter chromosomes? The answer lies in a branch of mathematics called topology. Simply put, topology concerns itself with shapes and its transformations under which certain properties remain unchanged. For a topology connoisseur, your body is equivalent to a doughnut because the alimentary canal runs through your body in the same way as the hole in a doughnut! Before we delve deeper into why bacterial DNA forms these concate-
mers when they replicate, we need to build some intuition about how topology plays out for certain circular shapes. Let us begin our adventure with a famous topological object called a Möbius strip, named after the German mathematician who studied it a couple of centuries ago. You can construct it by taking a strip of paper and simply twisting it by half a turn (180o) W C
C W
Figure 3: A Mobius strip is obtained by twisting a strip of paper by half a turn and gluing the ends.
before gluing the ends together (Figure 3). Now imagine taking a walk along this surface. If you keep at it, you will end at exactly the same place as you started. Take a moment to notice how bizarre that is compared to a regular paper strip—the Möbius strip only has 1 side! Now try cutting it through the middle along its length (you may want to get the scissors now, imagination may betray you). Instead of getting two separate rings, you will find just one ring but twice as long and half as wide. It has many other bizarre properties. These topological properties do not depend upon how long the strip of paper is, whether it is colored or not or if it is rough edged or smooth, etc. W C
W C
strand is a single continuous entity, in order to close the circle, ultimately both the W and the C strands need to join back onto itself (Figure 4). Now when DNA replicates, two parental strands unzip analogous to our experiment of taking a scissor and cutting through the middle of the strip. Through the process of DNA replication, each of the parental strand acts as a template to build the complementary strand. But since the parental strands started out being twisted onto each other, topological rules† demand that the two templates (and hence the two daughter DNAs) will have to remain linked, much like the two daughter strips in Figure 4. The inescapable fate of a circular double stranded DNA undergoing replication is that of permanent bondage. This is impending doom for the dividing bacterium, because ultimately the two chromosomes need to separate and partition such that the two resulting bacteria end up with one each.
which are subsequently relieved by topoisomerases. Although eukaryotic chromosomes are not circular and in theory should not be subjected to the same constraints, in reality, double stranded DNA held by proteins on either side form loops, which behave similarly to circular chromosomes. These enzymes are so critical in maintaining the topological dynamics of both bacterial and eukaryotic DNA that topoisomerase inhibitors are used as potent antibiotics and anti-cancer drugs. The connection between biology and topology runs deep and shows up at unexpected places. Closed, circular double-stranded DNA provide a simple yet compelling example of how certain kinds of shapes lead to unavoidable topological constraints. And yet, evolution, operating under the purview of physical laws, has found clever ways of getting around these issues and has made life possible ■ Footnotes:
Figure 4: Twisting a strip of paper by a full turn and gluing the ends reveals two interlocked rings.
If that was not surprising enough, I urge you to take another strip of paper and glue the ends but now with a full turn (360o) instead of a half turn (Figure 4). Again, cut through the middle along its length. Before you finish, take a moment and try to guess what it should look like. I was very surprised to find that the two rings remained linked with each other and there was no way of separating them without tearing either one. In this simplistic paper experiment, one full twist (T = 1) in the parent strip resulted in two daughter strips that pass through each other only once. This property of being “linked” is formally represented by the linking number* (L), which in this case is 1. If you dare to continue this process, you will see that for every full twist you add, you will end up with one more link after you have cut through the middle. This looks uncannily similar to what the circular daughter chromosomes look like after replication. Remember that DNA is made up of two strands that are wound over each other in a shape commonly known as the double helix. It so happens that a bacterial chromosome is a closed circle of these two strands, which we can name the Watson strand (W) and the Crick strand (C) for convenience. Since each
Biology has, as always, found a fix for this severe constraint that topology imposes by developing elegant molecular machines (enzymes). As we have seen from the paper experiments, the only way to unlink the two daughter chromosomes is to momentarily tear up one, pass one through the other and seal it back. That is exactly what a certain class of enzymes (known as Topoisomerases‡) manages to perform although at the expense of energy. These enzymes are brought into play every time a bacterium divides and are essential for cell division. Even in the absence of replication, the process of simply unwinding the two strands of circular double-stranded DNA (say for transcription) creates supercoiling§ (Figure 5),
* The linking number (Lk) is defined as the integer number of times one strand needs to pass through the other strand for them to be completely separated from each other. † This can be formally represented by the topological equation Lk = Tw + Wr, where Tw is the Twist and Wr is the Writhe. Twist is the number of helical turns of the DNA and Writhe measures the degree of supercoiling. In the absence of supercoiling (Wr = 0), Lk = Tw. ‡ There are two main classes of topoisomerases, those that nick one strand at a time (Topo I) and those that cause double-strand breaks (Topo II). § A change in twist (Tw) is compensated by an opposite change in Writhe (Wr) and vice versa such that the linking number (Lk) is kept constant. Hence unwinding a portion of any closed circular DNA causes supercoiling. Supercoiling is in itself a very interesting topic but I have not dealt with it here for simplicity.
i
i
ii i
ii
ii
Figure 5: Electron micrographs showing relaxed (i) and supercoiled (ii) closed circular DNA.
DISCOVERIES
Spatial Representation in Neuronal Populations Elizabeth Hutton / PhD Student, Watson School of Biological Sciences, CSHL
Self-localization and navigation is a complex neurological feat for higher organisms. An animal needs to both construct a mental map of its local environment, and continuously update its current position within that map. Surprisingly, researchers have discovered that this somewhat conceptual process is physically represented by a distinct set of neural cells known as place cells. The discovery of these place cells, and of the grid cells which program them, has provided a major insight into the creation of neural spatial representations. As recognized by this year’s Nobel Prize in Physiology or Medicine, this pathway offers a phenomenal model for understanding the mechanisms of information processing and memory. The original discovery of place cells uncovered an astounding system for generating a “mental map.” Each neuron in the network of place cells fires only when the test animal is in a set of specific locations, corresponding to a grid-like pattern1. Different combinations of these cells correspond to specific places within a given environment, so that
the entirety of a given area can be represented in the mind of the animal2. Amazingly, this mental map persists regardless of the animal’s path, direction of travel, or ability to see its surroundings. The same cells can participate in multiple “maps,” but do so in different combinations for each environment3. By maintaining a set map and varying the firing rate, these cells can further encode experience in a given location4. These neuronal patterns have been observed in animals all the way up to humans5, and their discoverer, John O’Keefe, received half of this year’s Nobel Prize. The other half of the Nobel Prize was awarded for the discovery of the mechanism for generating these mental maps. The place cells are in the hippocampus, which is not optimized for the computational work of establishing, updating, and correcting mental maps, and merely stores these mental maps using a relatively rigid signaling structure6. However, the adjacent region of the brain receives input from all sensory systems, and signals directly upstream of the place cells during map formation10. In 2004, the Moser husband-wife team discovered that the cells in this region, named “grid cells”, are individually capable of generating miniature maps7. By combining signals based on sensory input, these grid cells can collectively signal changing position8.
Grid cells appear to have a topographic organization8, and it has been hypothesized that anatomical clusters of grid cells represent maps of different locations9. While this grid map is anchored to environmental landmarks, it was discovered that self-motion is used to maintain and update grid representationsReviewed by 9,10. It is believed that sensory information is used to set the starting parameters of the grid and correct for errors, while speed and direction signals are used to generate and update the grid. The final map is then stored in the place cells. This is the first high-level neural representation to be understood at the cellular level. This system has enormous implications for informational processing and memory storage, and is an exciting intersection of network analysis and biology ■ References 1. O’Keefe & Dostrovsky, Brain Res, 1971 2. O’Keefe & Burgess, Nature, 1996 3. Wilson & McNaughton, Science, 1993 4. Leutgeb et al., Science, 2005 5. Jacobs et al, Nat. Neurosci, 2013 6. McNaughton et al., Exp. Brain Res, 1989 7. Fyhn et al, Science, 2004 8. Hafting et al., Nature, 2005 9. Moser et al., Annu. Rev. Neurosci., 2008 10. Fyhn et al., Nature, 2007
INTERVIEW
Dr. Siddartha Mukherjee Robert Aboukhalil / PhD Student, Watson School of Biological Sciences, CSHL
There aren’t very many scientists whose claim to fame includes writing a best-selling, Pulitzer Prize-winning and Oprah-endorsed book. I had the good fortune to sit down with one such scientist, Siddartha Mukherjee, author of The Emperor of All Maladies: A Biography of Cancer. Siddartha is an Assistant Professor of Medicine at Columbia and a physician at Columbia University Medical Center, where his work is focused on leukemia. What prompted you to write the book? At the time, I was a fellow in oncology and became progressively convinced that we had no roadmap for cancer. Ultimately, I was asked by a patient to explain the current state of cancer research and where we were going next. Looking at volumes of books, I couldn’t find very many that offered a bird’s eye view of cancer research; those that did
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We have documents from ancient Egypt that describe cases consistent with contemporary descriptions of breast cancer.
were written by authors pushing for a particular direction in cancer research. They were written as polemics, whereas I wanted to write a biography of cancer.
As scientists, we struggle with science communication. How did you approach that writing process? I hate jargon because I think people sometimes use it to obfuscate the fact that they don’t understand something. At a more global level, good scientists are usually incredibly good writers because they can communicate the simplicity of their thinking. There’s no reason whatsoever that a good scientist shouldn’t be a good writer because the process of thinking is usually extremely transparent and should be extremely easy to explain to someone.
Did your training as a physician help in that regard as well? I think good doctors can be good writers for other reasons as well, so I think I relied on that a lot and I continue to rely on that, and I think unfortunately there are aspects of our education that beat that out of us, and it’s nice to return back to them, back to having a real conversation as opposed to obfuscating and being caught in jargon.
In your book, you talk about how cancer is actually an old disease; when was cancer first described? Interestingly, the earliest descriptions of cancer go back to the very first medical documents we have. For example, we have documents from ancient Egypt that describe cases consistent with contemporary de-
scriptions of breast cancer. These records are incredible because they read like contemporary medical documents. The physiology may have been wrong and the therapeutics misguided, but the organization of disease into mechanism and the treatment being driven by mechanism is an ancient idea.
Do these documents describe any treatments? For breast cancer, the original recommendation was to do nothing because there was no treatment. Slowly, that evolved into surgery. We know there were attempts at breast surgery for cancer very early on. For example, there’s a description by Herodotus [Greek historian, 5th century B.C.] of a queen having what seems to be a breast cancer removed.
In 1971, the National Cancer Act was signed and the “War on Cancer” began. How did it start and how have we fared so far? It started as a massive campaign organized by very prominent scientists and philanthropists. There was a feeling that tackling cancer would work like the moon landing or the Manhattan project did—that if you poured resources into a problem and made it a consolidated effort, there would be a common cause and ultimately, a common cure.
Looking back, was it too naïve and ambitious? It was naïve in some ways, ambitious in others, but it also had many collateral ad-
vantages. The biggest advantage was that it created a landmark, which was useful for measuring our progress. On the flip side, the War on Cancer created a series of unnatural expectations around what was achievable and what wasn’t. When it was not achieved, it created a cycle of disappointment. It was a mixed blessing, but I do think we wouldn’t be here today if it wasn’t for the War on Cancer. On the other hand, I feel as though we would be in a different place in terms of public trust if the War on Cancer had not been executed the way it had.
Did the War on Cancer take focus away from cancer prevention research? There is some truth to that perhaps. I think historically, cancer prevention was in a different space in the 1970’s than it is today. Part of the appropriate embracement of cancer prevention has been in the light of our failure to treat and cure many cancers, so a rhetoric of cure definitely masked some of the rhetoric of prevention, although prevention research was eventually ramped up by the National Cancer Institute.
What does the landscape of cancer look like today? To me, the landscape is becoming very granular: targeted therapies, immunotherapy, multidrug trials, vaccines, etc. It seems we’re once again in the thick of things and it would be helpful for us to take a step back and ask where we’re going. One of the reasons for writing the book was to hopefully initiate a
conversation about taking a bird’s eye view and ask: “What has really changed? What do we know now that we didn’t know before? Should we now reorient our efforts?”
What is the next step in moving forward with cancer research? First, we need to focus on cancers for which we really have no understanding whatsoever, and try to deepen our molecular understanding. be done at a basic research level. For cancers where we have some understanding and there exists a multiplicity of therapies, we must try to integrate them in a sensible way. That’s probably a more translational project than basic science. Another important aspect moving forward is to integrate epidemiological approaches with other sciences to develop better models of predicting risk. Moreover, goal we still haven’t met is to reduce access disparities to treatments that are known to work, such as surgery, chemotherapy, targeted therapy, and prevention. Finally, I think we should re-focus our attention on palliation, pain control, pain relief and discussions around death and dying, which are part and parcel of cancer. The next step starts with basic science, and ends with the humanistic aspects of medicine ■
Cold Spring Harbor Laboratory 2015 Meetings & Courses Meetings
Biology and Genomics of Social Insects
Cell Death
Systems Biology: Global Regulation of Gene Expression
The Biology of Genomes
Genome Engineering: The CRISPR/Cas Revolution
The Biology of Cancer: Microenvironment, Metastasis & Therapeutics
September 24 - September 27 abstracts due July 3
Cellular Dynamics & Models
Retroviruses
Stem Cell Biology
80th Symposium: 21st Century Genetics Genes at Work
Probabilistic Modeling in Genomics
January 28 - February 1 abstracts due November 18 March 3 - March 6 abstracts due January 9
Exercise Science & Health
March 9 - March 12 abstracts due January 9
Systems Biology: Networks
March 17 - March 21 abstracts due January 16
Wiring the Brain
March 24 - March 28 abstracts due January 23
Patenting in the Life Sciences: The Patentability of Self-Replicating Systems March 30 - April 2
RNA & Oliogonucleotide Therapeutics April 8 - April 11 abstracts due February 6
Fundamental Immunology and Its Therapeutic Potential April 14 - April 18 abstracts due January 23
The Ubiquitin Family
April 21 - April 25 abstracts due January 30
Telomeres & Telomerase
April 28 - May 2 abstracts due February 6
May 2 - May 5 abstracts due February 13 May 5 - May 9 abstracts due February 13
May 12 - May 16 abstracts due February 20 May 18 - May 23 abstracts due February 27
May 26 - May 31 abstracts due March 6
The Evolution of Sequencing Technology: A Half-Century of Progress July 16 - July 19
September 15 - September 19 abstracts due June 26
Neurobiology of Drosophila
September 29 - October 3 abstracts due July 10 October 7 - October 11 abstracts due July 17 October 14 - October 17 abstracts due July 24
Genome Informatics
October 28 - October 31 abstracts due August 14
Cell Biology of Yeasts
November 3 - November 7 abstracts due August 21
Metabolic Signaling and Disease: From Cell to Organism
Single Cell Analyses
Eukaryotic mRNA Processing
Behavior & Neurogenetics of Nonhuman Primates
August 11 - August 15 abstracts due May 22 August 18 - August 22 abstracts due June 2
Mechanisms of Eukaryotic Transcription August 25 - August 29 abstracts due June 5
Eukaryotic DNA Replication & Genome Maintenance
September 1 - September 5 abstracts due June 12
Microbial Pathogenesis and Host Response
November 11 - November 14 abstracts due August 28
November 17 - November 20 abstracts due September 4
Plant Genomes & Biotechnology: From Genes to Networks
December 2 - December 5 abstracts due September 18
Rat Genomics & Models
December 9 - December 12 abstracts due September 25
September 8 - September 12 abstracts due June 19
Autumn morning view of Cold Spring Harbor Laboratory, New York
Courses
Statistical Methods for Functional Genomics
Imaging Structure & Function in the Nervous System
Workshop on Leadership in Bioscience
Workshop on Pancreatic Cancer
March 13 - March 16
Protein Purification & Characterization April 8 - April 21
Quantitative Imaging: From Cells to Molecules April 8 - April 21
Cell & Developmental Biology of Xenopus: Gene Discovery & Disease April 9 - April 21
Single Cell Analysis June 3 - June 16
Advanced Bacterial Genetics June 3 - June 23
Ion Channels & Synaptic Transmission June 3 - June 23
Mouse Development, Stem Cells & Cancer June 3 - June 23
Workshop on Autism Spectrum Disorders June 4 - June 10
June 18 - July 1
July 21 - August 10
June 24 - June 30
Synthetic Biology
Drosophila Neurobiology: Genes, Circuits & Behavior
Cellular Biology of Addiction
June 26 - July 16
Frontiers & Techniques in Plant Science June 26 - July 16
Advanced Techniques in Molecular Neuroscience June 30 - July 16
Vision: A Platform for Linking Circuits, Perception and Behavior
July 27 - August 10
August 4 - August 10
Programming for Biology October 12 - October 27
X-Ray Methods in Structural Biology October 12 - October 27
Computational & Comparative Genomics October 28 - November 3
Antibody Engineering & Phage Display
July 7 - July 20
November 9 - November 22
Proteomics
Advanced Sequencing Technologies & Applications
July 14 - July 27
Eukaryotic Gene Expression
November 10 - November 22
Yeast Genetics & Genomics
March 30 - April 1
July 21 - August 10 July 21 - August 10
The Genome Access Course
November 16 - November 18
www.cshl.edu/meetings