Inside the Marder Lab

Marder Office MobileProfessor Eve Marder’s office door is unmistakable. Tucked between the certificates, accolades, official photos, and award plaques that plaster her lab’s walls, her office door is decorated with a collage of fading photos of students and yellowing cartoons of lobsters and crabs. Inside the office, the shelves are crammed with neuroscience books and stacks of primary and review articles published by her lab throughout her career. But among all of the awards and publications there’s something else that draws your eye. Hanging just above her computer is a homemade mobile built by a former student. Dangling from the mobile are photos of lab members and important scientific figures, faces and images gently pirouetting and circling around one another just above Marder’s head.

Now Marder has another award to add to her vast collection. In June 2016, she was announced as a winner of the Kavli Prize in Neuroscience. Marder shares the Prize with Carla Shatz, of Stanford University, and Michael Merzenich, of the University of California, San FMarder Office Doorrancisco. The award was given to these scientists “for the discovery of mechanisms that allow experience and neural activity to remodel brain function.” The Prize includes a gold medal ceremony and a one-million-dollar award (to be split among the winners), which will be conferred by His Majesty King Harald V of Norway in Oslo in September 2016. First awarded in 2008, the Kavli Prize was established to recognize scientific achievement and to honor creative scientists in the fields of Neuroscience, Astrophysics, and Nanoscience.

The illustrations of lobsters and crabs on Marder’s office door pay homage to the creatures that her lab has used as research subjects to shed light on the fundamental rules that govern how nervous systems function. Her life’s work has been studying a group of neurons called the stomatogastric ganglion (STG). These neurons control rhythmic chewing and filtering of food through the stomachs of crustaceans like crabs and lobsters. The STG is a relatively small (~30 neurons) circuit of cells. It can be dissected out from the animal and placed in a dish, where it can continue to function for up to weeks at a time. In the dish, the neurons will continue to produce electrical rhythms as if the stomach were still chewing and filtering. These electrical rhythms can be studied using a technique called electrophysiology where changes in cell voltage are measured and recorded. The STG contains well-studied central pattern generators (CPGs), circuits that produce rhythmic patterns without sensory feedback. In fact, insight gained from studying the general principles involved in STG activity has given neuroscientists a better understanding of CPGs involved in human behaviors including walking, sleeping, and breathing.

pyloric rhythm

From The Cancer borealis STG guide (Rutgers University)

Because the STG is robust and relatively simple, it makes an excellent model to study how neural circuits work. Gina Turrigiano, a colleague at Brandeis, has written that the ideas Marder and her lab developed from studying this system have “catalyzed paradigm shifts in fields as diverse as neural circuit function, computational neuroscience, and neuronal homeostasis…Her ideas have proved to be highly generalizable, and have fundamentally changed the way neuroscientists think about these problems.”

Neuroscientists used to think that the brain was wired like an electronic circuit board. In other words, neurons were wired together via simple connections that could only be “on” or “off.” When all the connections were turned on, the circuit produced a single behavior. Understanding the brain was thought to be as simple as determining how each neuron was physically connected to all others. While working as a graduate student at the University of California San Diego, Marder made a discovery that questioned this dogma. She found that neurons in the STG release acetylcholine in addition to the already known neurotransmitter, glutamate. This result, published in 1974, suggested that neuronal connections could be turned on in more than one way. Her discovery was instrumental in shifting how neuroscientists think about nervous systems. It could no longer be assumed that a simple connection diagram was sufficient.

Further work uncovered many different neuromodulators (neurotransmitters and peptides hormones) that could modulate or alter the neurons’ rhythms of the STG. Dr. Marder found that release of these neuromodulators could shift the activity of the neural circuit without changing any physical connections. This shift can happen very quickly and be long lasting. In addition, neuromodulation can also induce certain neurons to synchronize with different circuits switching their activity to coordinate with one circuit (like the ‘chewing’ circuit) and then to another (like the ‘filtering’ circuit). Both of these findings opened new questions for the entire field of neuroscience. A neural circuit with the same physical connections could have many different output activities so that even simple neural circuits could accomplish a surprising variety of tasks.

Partial Summary of Neuromodulation of the STG, see Marder (2012) Neuron 76:1–11.

Much of the Marder lab’s work in recent years has grown from this initial work in neuromodulation. With so much flexibility of activity, it became important to explore how these systems are able to maintain stability. Although a neuron can live over 100 years, the components of that neuron, including proteins that make up ion channels, constantly change on a timescale of seconds to weeks. Marder worked in collaboration with Larry Abbott and his lab to study how neurons maintain appropriate activity despite such rapid turnover. This work resulted in theoretical models suggesting that neurons have an intrinsic “set-point.” An individual neuron mediates changes in ion channels to produce a specific desirable activity output. This work informed our understanding of how neurons and nervous systems are able to be both plastic, but also to remain functional in a constantly changing environment. It has given rise to work investigating how synapses are able to respond to changing activity or “synaptic scaling” and research into how neurons determine their “set-point” at a molecular level.

Many of the numerous primary and review papers stacked in Marder’s office have been co-authored by some of her almost 80 graduate students and post-docs. These papers have been the work of both experimentalists, who gather data from real neurons, and theorists, who use computers to make hypothetical models of neurons. The collaborative working environment lends strength to the work completed in the Marder lab and forces students and post-docs to explain their work to peers with very different skill sets. It also gives lab members an opportunity to use both theory and experiments to cooperatively build stronger models and to design better experiments. As one example of this, Marder and Abbott together developed the dynamic clamp tool. Using this tool, real biological neurons are connected to model neurons generated within computer programs. This system, now used by scientists all over the world, makes well-controlled manipulations while still probing a dynamically complex biological system.

Wandering through the Marder lab on any given day, it is always buzzing with students and postdocs at computers, doing dissections, or popping into Marder’s office for a quick chat and some chocolate. Currently, the Marder lab is investigating variability in neural circuits. Scientists often view variability as a result of experimental error and attempt to minimize it through averaging over multiple trials. Marder’s approach has revealed that variability is a natural part of how neurons and circuits are constructed and can reveal very important information about how these systems work. Both experimental and theoretical work from the Marder lab has shown that neurons with widely varying characteristics can exhibit nearly identical activity patterns. Thus rather than finding the average properties of a neuron, it is crucial to understand how functionality is maintained in the presence of this variability.

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Dye fill of STG neuron by Marder lab members

One way the Marder lab currently studies this variability is using temperature change, a physiologically relevant stimulus for crabs who live in varying depths of water throughout the year. Understanding more about how different neuromodulators affect the activity rhythm continues to be an ongoing project since approximately 50 neuromodulators have been discovered in the STG. Other lab members are interested in observing variability in the morphology of different cell types. STG neurons visually have a cell body with a single axon that branches many times so that the cells look less like a traditional ‘neuron’ image but rather a cell body connected to something that looks like a tangled ball of hair. Other work in the lab is interested in investigating where different ion channels are located on this highly branched and complex structure.

To those scientists who have met Dr. Marder she is a source of inspiration and advice. She clearly enjoys engaging with younger scientists especially graduate students and postdocs and many of them have experienced her mentorship throughout their careers. Barbara Beltz of Wellesley College wrote of Marder “It has been clear to me for a long time that although I had PhD and postdoctoral advisors who were supportive and kind, it was Eve who was the most influential mentor in my career.” Marder provides supportive encouragement always paired with frank honesty sometimes in the form of tough love. Ted Brookings, a former Marder lab post-doc says that Marder takes mentorship very seriously and her greatest pride as an advisor is not in selecting the most brilliant people but instead seeing the evidence of how much they have grown during their time in the lab. Many female scientists in particular see her as a trail-blazer and those who have been to her office find the life-sized cutout of Xena Warrior Princess to be appropriate decor.

Working at her undergraduate alma mater, Brandeis University since 1978, Marder helped to build one of the first undergraduate neuroscience programs in the country and a highly regarded neuroscience PhD program. Even as a senior professor, Marder often teaches the Principles of Neuroscience course taken by upper-level undergraduates and required for incoming graduate students. She is unique among the faculty for teaching the course using the blackboard rather than Powerpoint and begins each year with a new bucket of large colorful sidewalk chalk. According to a former Marder lab graduate student, Marder’s teaching permeates everything she does, whether she’s in front of the classroom, having a personal sit down in her office or giving a grand seminar.

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Celebration party after Kavli Prize 2016 announcement. Photo by Steven Karel.

Marder received hundreds of congratulatory emails from colleagues and former students and post-docs after the announcement of the Kavli Prize. The extensive body of research from Marder and her students, using the STG, has revealed fundamental properties that apply to all nervous systems. One of her colleagues at Brandeis University, Leslie Griffith has written “Her work has provided a platform for much of our current cellular understanding of circuit function and stability and the mechanisms by which circuits negotiate the flexibility/stability trade-off.” The homemade mobile rotating above her head in her office appears to capture the essence of how Marder views her work and her lab – old and new people constantly in motion orbiting groundbreaking discoveries in neuroscience.

Drawing by Ben Marder

Drawing by Ben Marder

 

 

About the Author

Maria Genco is a PhD candidate in the Neuroscience Program working in the Griffith Lab at Brandeis University.

Jeffery Kelly to receive the 2016 Jacob and Louise Gabbay Award

jefferywkelly

Jeffery W. Kelly

Jeffery W. Kelly, the Lita Annenberg Hazen Professor of Chemistry, and Chairman of the Department of Molecular and Experimental Medicine at the Scripps Research Institute, has been selected to receive the 2016 Jacob and Louise Gabbay Award in Biotechnology and Medicine “in recognition of his profound and paradigm-shifting contributions to our understanding of protein folding mechanisms and protein misfolding diseases”.

The award, administered by the Rosenstiel Center at Brandeis, consists of a $15,000 cash prize and a medallion. Dr. Kelly will deliver the award lecture on “The Chemistry and Biology of Adapting Proteostasis for Disease Intervention” in the Shapiro Campus Center Theater at 4:00PM, on Thursday, September 29, 2016.

The Kelly Group focuses their research on understanding the principles of protein folding and comprehending the basis for misfolding diseases. They strive to develop novel therapeutic strategies using chemistry, biophysical and cell biology approaches.

 

Two Science Students Are Fulbright Fellows

Two of the five Brandeis undergraduates and recent alumni that have been selected to teach English overseas as Fulbright Fellows are Division of Science students.

Abby Brooks ’16 and Joel Burt-Miller ’16 have received English Teaching Assistantships through the Fulbright grant program. Brooks is a double major in biology and history. She will be teaching in Laos. Joel Burt-Miller ’16 is a double major in biology and Health: Science, Society and Policy. He will be teaching in India.

Find more information about our soon-to-be graduates and the Fulbright program on BrandeisNow.

7th Annual Jay Pepose Award to be presented April 12 at 12:30 pm

David WilliamsDavid Williams from the University of Rochester has been selected to receive the 7th annual Jay Pepose ’75 Award in Vision Sciences. Williams will be presented with the Pepose award on Tuesday, April 12th at 12:30 pm in Gerstenzang 121. The celebration will include David Williams talk titled, “Seeing Through the Retina”.

Williams’ research has improved the effectiveness of laser refractive surgery, the design of contact lenses, and enabled the imaging of single cells in the retina.

Yoshinori Ohsumi to Receive Rosenstiel Award Wednesday, April 6

ohsumi220Biologist Yoshinori Ohsumi will receive the 45th Rosenstiel Award for Distinguished Work in Biomedical Science this Wednesday, April 6th at 4:00 pm in Gerstenzang 123. At that time, he will present a lecture titled, “Lessons from yeast: Cellular recycling system, autophagy”.

Ohsumi is a cell biologist and professor at the Tokyo Institute of Technology’s Frontier Research Center in Japan. He is one of leading experts in the world on autophagy, a process that allows for the degradation and recycling of cellular components. The Rosenstiel Award is being given to Ohsumi in recognition of his pioneering discoveries in autophagy.

Learn more about Professor Ohsumi and his research at BrandeisNow.

Four Brandeis Science Grads Receive 2016 NSF Graduate Fellowships

GRFP_logoA science education at Brandeis University can be a springboard to future science achievements. We would like to congratulate four of our science graduates who have received the prestigious National Science Foundation Graduate Research Fellowships for 2016.

Noam Saper

Noam was an outstanding student graduating summa cum laude with highest honors in Chemistry in 2015. At Brandeis, Noam worked in the labs of Prof. Barry Snider and Prof. Christine Thomas. He co-authored 3 publications with Snider and Thomas.

Noam received multiple awards including the Barry M. Goldwater Scholarship (2014); the Elihu A. Silver Prize (2014); and the Doris Brewer Cohen Endowment Award (2015).

Following graduation and enthralled by the mysteries of the west coast, he decided to attend the University of California, Berkeley. Noam is working on mechanistic studies of Ni-catalyzed diaryl ether hydrogenolysis in Professor John Hartwig’s laboratory.

Alexandra Sun

Another outstanding Chemistry student, Alexandra Sun graduated magna cum laude with highest honors in 2015. Alexandra also worked in Christine Thomas’ lab where she carried out research on Transition Metal Complexes Featuring a Redox-Active Bidentate Amido-Phosphido Ligand. Alexandra received the Melvin M. Snider Prize in Chemistry in 2015.

She is currently a first-year student in the Chemistry Department at the University of Michigan working with Professor Corey Stephenson on developing new methods in photoredox catalysis.

Abigail Zadina

Abigail received her BS/MS in Neuroscience in 2013. Working in Michael Rosbash’s lab, she was a co-author on 2 publications and received numerous awards including the Doris Brewer Cohen award and the Elihu Silver Prize. In 2013, Abigail discussed her science experience in the Brandeis publication Imprint.

Following graduation, Abigail worked at Columbia in Richard Axel’s lab. She is currently a PhD student in Neurobiology and Behavior at Columbia University.

Joseph Jacobowitz

Joseph Jacobowitz received his BS/MS in 2014, graduating summa cum laude with Highest Honors in Biochemistry. While a Brandeis undergraduate, Joseph co-authored a publication with his faculty mentor, Doug Theobald. In 2013, Joseph received the Division of Science Prize for Outstanding Research Accomplishment and the William P. Jencks  Award in Biochemistry in 2014.

Joseph is in the Biology PhD program at MIT, working for Jing-Ke Weng on the origins of chemodiversity in plants.

Summer Research at Brandeis

All four science graduates had the opportunity to jump start their careers by doing summer research at Brandeis. Noam, Alexandra and Joseph were Division of Science Summer Undergraduate Research Fellows (SURF). Abigail received a Computational Neuroscience Traineeship.

These undergraduate research programs enable students to spend their summers at Brandeis engaged in intensive undergraduate training and summer research. Both programs provide a stipend, faculty mentoring and full-time lab research. The Summer Undergraduate Research Fellows work culminates in a poster presentation summarizing their work. The SURF program is funded by generous donations from alumni. The Computational Neuroscience Traineeship program begins in the summer and runs through the following academic year. It is funded through a grant from the National Institute on Drug Abuse. 

Research Funding For Undergrads: Div Sci SURF

The Division of Science announces the opening of the Division of Science Summer Undergraduate Research Fellowship competition for Brandeis students doing undergraduate research in Summer 2016.  These fellowships are funded by generous alumni donations.

The due date for applications  is February 24, 2016,  at 6:00 PM EST.

Division of Science Summer Undergraduate Research Fellows will receive $5000 in stipend support to do summer research (housing support is not included). Students who will be rising Brandeis sophomores, juniors, or seniors in Summer 2016 (classes of ’17, ’18, and ’19), who in addition are working in a lab in the Division of Science at the time of application, are eligible to apply. A commitment from a Brandeis faculty member to serve as your mentor in Summer 2016 is required.

The Division of Science Summer Program will run from May 31 – Aug 5, 2016. Recipients are expected to be available to do full time laboratory research during that period, and must commit to presenting a poster at the final poster session (SciFest VI) on Aug 4, 2016.

The application form is online (Brandeis login required). Questions that are not answered in the online FAQ may be addressed to Steven Karel <divsci at brandeis.edu>.

There will be a question-and-answer session about summer research funding applications on Thursday, Jan 14 at 5 pm in Gerstenzang 123

Research Funding for Undergrads: M. R. Bauer Fellows

The Division of Science is pleased to announce that a generous gift from the M. R. Bauer Foundation will fund ten M. R. Bauer Foundation Summer Undergraduate Research Fellows (“M. R. Bauer Fellows”) in Summer 2016. The due date for applications  is February 24, 2016 at 6:00 PM EST. 

M. R. Bauer Fellows will receive $5000 as a stipend in support of their summer research (housing support is not included). Students who will be rising Brandeis sophomores, juniors, or seniors in Summer 2016 (classes of ’17, ’18, and ’19), are eligible to apply. A commitment from a Brandeis Division of Science faculty member to serve as mentor in Summer 2016 on a project leading to a senior thesis is required.

The Division of Science Summer Program will run from May 31 to Aug 5, 2016. M. R. Bauer Fellows are expected to be available to do full time laboratory research during that period, and must commit to presenting a poster at the final poster session (SciFest VI) on August 4, 2016. M.R. Bauer Fellows are also expected to give back to the University in ways that promote science and research.

The application form is online (Brandeis login required). Questions that are not answered in the online FAQ may be addressed to Steven Karel <divsci at brandeis.edu>.

IMG_1293The M.R. Bauer Foundation has been a generous and steadfast friend of the Volen National Center for Complex Systems for over 20 years. Established at Brandeis University in 1994, the Volen Center brings together faculty, students and postdocs from across the sciences with a common goal of understanding the brain, from the level of molecules to cognition.

The foundation recognizes that the advancement of science takes place not only in the lab, but in the seminar room and lecture hall, and in the countless conversations that help to spread ideas and spark new research. The size and intimate setting of the Volen Center has made it an ideal environment for forging connections among investigators from diverse fields.  A central part of these connections is the M.R. Bauer Foundation Colloquium Series, Distinguished Lecturer Series, and Annual Scientific Retreat program. This support has now been substantially widened through this new program of supporting undergraduates in summer research, which will enable greater participation by the youngest group of Brandeis researchers.

There will be a question-and-answer session about summer research funding applications on Thursday, Jan 14 at 5 pm in Gerstenzang 123

 

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