Division of Science Hosts the 2016 Undergraduate Science Symposium

Written by Jena Pitman-Leung.

uss-img1

The Division of Science Graduate Affairs group hosted the 2nd annual Brandeis University Undergraduate Science Symposium on Saturday 17th, 2016. More than 60 students representing institutions from Massachusetts, Rhode Island, and New Hampshire attended the event, which was held in the Shapiro Science Center. The morning session included research talks from faculty in the Life Sciences (Don Katz, Liz Hedstrom) and the Physical Sciences (Matt Headrick, Christine Thomas), followed by panel discussions with faculty in the Life Sciences (Liz Hedstrom, Bruce Goode, and Maria Miara) and Physical Sciences (Gabriella Sciolla, Isaac Krauss, Jordan Pollack) on how to apply to graduate school. The students then came together for a networking lunch with Brandeis students, postdocs, and faculty. Lunch was followed by a well attended poster session, where 38 students had the opportunity to present their independent research. The day ended by awarding prizes for the best posters in five disciplines. The winners were:

Biology: Rahim Hirani, Hampshire College, “The regulatory role of Beta-Arrestin 1 in prostate cancer cell proliferation”
Neuroscience: Paige Miranda, Wellesley College, “Metabolic Processes Driving Hippocampal Long Term Potentiatio”
Biochemistry: Myfanwy Adams, Wellesley College, “Expression of a Cardiac ATP-sensitive Potassium Channel in a Heterologous Cell Line”
Chemistry: Natsuko Yamagata, Brandeis University, “Exploring the Unexplored: Supramolecular Hydrogels of Retro-Inverso Peptides for 3D Cell Culture”
Physics: Jameson O’Reilly, Northeastern University, “A capillary-mimicking optical tissue phantom for diffuse correlation spectroscopy”

The Division of Science is committed to supporting local undergraduate research, and is excited about the possibility of these bright young scientist choosing Brandeis for their graduate study. We look forward to hosting similar events in the future!

Recycling is good for your brain

If you were able to remember where you put your keys on your way out the door this morning, it’s because – somehow – synapses in your brain changed their properties to encode this information and store it until you needed it. This process, known as “synaptic plasticity”, is essential for the continuity of our memory and sense of self, and yet we are only beginning to grasp the molecular mechanisms that enable this amazing feat of constant information storage and retrieval. Now a collaborative paper from the Turrigiano and Nelson labs just published in Cell Reports sheds important new light into how experience interacts with the genome to allow synapses to change their strength to store information.

Synapses are the connections between neurons, and it has long been appreciated that information is stored in large part through changes in the strength of these connections. Changes in strength at many synapses are in turn determined by the number of neurotransmitter receptors that are clustered at synaptic sites – the more receptors synapses have, the easier it is for neurons to excite each other to transmit information. Synapses are highly complicated molecular machines that utilize at least 300 different proteins that interact to traffic these receptors to synapses and sequester them there, and exactly how a change in experience alters the function of this nano-machine to enhance the number of synaptic receptors is still a matter of puzzlement.

In this study the Brandeis team devised a way to screen for candidate proteins that are critical for a particular form of synaptic plasticity: “synaptic scaling”, thought to be especially important for maintaining brain stability during learning and development. They were able to induce synaptic scaling within specific labelled neurons in the intact mouse brain (layer 4 star pyramidal neurons), and then sort out those labelled neurons from the rest of the brain and probe for changes in gene expression that were correlated with (and potentially causally involved in) the induction of plasticity.  This approach produced a small number of candidate genes that were up- or down-regulated during plasticity, to produce more or less of a given protein.  The team then went on to show that – when upregulated – one of these candidates (known as µ3A) acts to prevent neurotransmitter receptors from going into the cellular garbage bin (the lysosomes, where proteins are degraded) and instead recycles them to the synapse. Thus increased µ3A flips a switch within cells to enhance receptor recycling, and this in turn increases synaptic strength.

µ3A plays a critical role in the recycling of AMPA-type neurotransmitter receptors

A screen for genes with altered expression during synaptic plasiticity in specific neurons revealed that µ3A plays a critical role in the recycling of AMPA-type neurotransmitter receptors at the synapse. When this protein is upregulated, it prevents receptors from being trafficked into lysosomes, and instead allows them to be recycled back to synapses, increasing synapse number and enhancing synaptic strength.

It turns out that many other forms of synaptic plasticity use the same receptor recycling machinery as synaptic scaling, so it is likely that this mechanism represents  an important and general way for neurons to alter synaptic strength. This study also raises the possibility that defects in this pathway might contribute to the genesis of neurological disorders in which the stability of brain circuits is disrupted, such as epilepsy and autism. So next time you complain about having to sort your garbage, consider that your neurons do it all the time –  and what’s good for the planet turns out to be good for your brain as well.

Steinmetz CC, Tatavarty V, Sugino K, Shima Y, Joseph A, Lin H, Rutlin M, Lambo M, Hempel CM, Okaty BW, Paradis S, Nelson SB, Turrigiano G. Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway. Cell reports. 2016.

Neurons that make flies sleep

Sleep is known to be regulated by both intrinsic (what time is it?) and environmental factors (is it hot today?). How exactly these factors are integrated at the cellular level is a hot topic for investigation, given the prevalence of sleep disorders. Researchers in the Rosbash and Griffith labs are pursuing the question in the fruit fly Drosophila melanogaster, to take advantage of the genetic tools in the model system and the excellent understanding of circadian rhythms in the fly.

Like other animals, the fruit fly displays a robust activity/sleep pattern, which consists of a morning (M) activity peak, a middle-day siesta, an evening (E) activity peak and nighttime sleep. M and E peaks are controlled by different subgroups of circadian neurons such as wake-promoting M and E clock cells.

In a paper just published in Nature, Brandeis postdoctoral fellow Fang Guo and coworkers identify a small group of circadian neurons, a subset of the glutamatergic DN1 (gDN1s) cells, which have a critical role in both types of regulation. The authors manipulated the gDN1s activity by using recently developed optogenetics tools, and found activity of those neurons is both necessary and sufficient to promote sleep.

circadian-feedback

The cartoon model illustrates how the circadian neuron negative feedback set the timing of activity and siesta of Drosophila. The arousal-promoting M cells (sLNv) release pigment-dispersing factor (PDF) peptide to promote M activity at dawn. PDF peptide can activate gDN1s, which release glutamate to inhibit arousal-promoting M and E (LNds) cells and cause a middle-day siesta. At evening, the gDN1s activity is reduced to trough levels and release E cell activity from inhibition.

DN1s enhance baseline sleep by acting as feedback inhibitors of previously identified wake-promoting M and E clock cells, making them the first known sleep-promoting neurons in this circadian circuit. It is already known that M cell can activate gDN1s at dawn. Thus the daily activity-sleep pattern of Drosophila is timed by the circadian neuron negative feedback circuitry (see Figure).  More interestingly, by using in vivo calcium reporters, the authors reveal that the activity of the gDN1s is also shown to be sexually dimorphic, explaining the well-known difference in daytime sleep between males and females. DN1s also have a key role in mediating the effects of temperature on daytime sleep. The circadian and environmental responsiveness of gDN1s positions them to be key players in shaping sleep to the needs of the individual animal.

Authors on the paper include postdocs Guo, Junwei Yu and Weifei Luo, staff member Kate Abruzzi, and Brandeis graduate Hyung Jae Jung ’15 (Biology/HSSP).

Guo F, Yu J, Jung HJ, Abruzzi KC, Luo W, Griffith LC, Rosbash M. Circadian neuron feedback controls the Drosophila sleep-activity profile. Nature. 2016.

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.

Picture2

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.

IMG_1984 (1)

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.

Marder, Shatz, and Merzenich share 2016 Kavli Prize in Neuroscience

Eve MarderBreaking news: The 2016 Kavli Prize in Neuroscience is awarded to Eve Marder (Brandeis), Carla Shatz (Stanford), and Michael M. Merzenich (UCSF), “for the discovery of mechanisms that allow experience and neural activity to remodel brain function.”

 

Trapping individual cell types in the mouse brain

Lines labeling cortical subplate, mesencephalic, and diencephalic cell types

Lines labeling cortical subplate, mesencephalic, and diencephalic cell types (see Fig. 7 in Shima et al.)

The complexity of the human brain depends upon the many thousands of individual types of nerve cells it contains. Even the much simpler mouse brain probably contains 10,000 or more different neuronal cell types. Brandeis scientists Yasu Shima, Sacha Nelson and colleagues report in the journal eLife on a new approach for genetically identifying and manipulating these cell types.

Cells in the brain have different functions and therefore express different genes. Important instructions for which genes to express, in which cell types, lie not only in the genes themselves, but in small pieces of DNA called enhancers found in the large spaces between genes. The Brandeis group has found a way to highjack these instructions to express other artificial genes in particular cell types in the mouse brain. Some of these artificially expressed genes (also called transgenes) simply make the cells fluorescent so they can be seen under the microscope. Other transgenes are master regulators that can be used to turn on or off any other gene of interest. This will allow scientists to activate or deactivate the cells to see how they alter behavior, or to study the function of specific genes by altering them only in some cell types without altering them everywhere in the body. In addition to developing the approach, the Brandeis group created a resource of over 150 strains of mice in which different brain cell types can be studied.

website: enhancertrap.bio.brandeis.edu

Shima Y, Sugino K, Hempel C, Shima M, Taneja P, Bullis JB, Mehta S, Lois C, Nelson SB. A mammalian enhancer trap resource for discovering and manipulating neuronal cell types. eLife. 2016;5.

Fruit flies alter their sleep to beat the heat

Do you have trouble sleeping at night in the summer when it is really hot?

Does a warm sunny day make you want to take a nap?

You are not alone — fruit flies also experience changes in their sleep patterns when ambient temperature is high. In a new paper in Current Biology, research scientist Katherine Parisky and her co-workers from the Griffith lab show that hot temperatures cause animals to sleep more during the day and less at night, and then investigate the mechanisms governing the behavior.

The increase in daytime sleep is caused by a complex interplay between light and the circadian clock. The balance between daytime gains and nighttime losses at high temperatures is also influenced by homeostatic processes that work to keep total daily sleep amounts constant. This study shows how the nervous system deals with changes caused by environmental conditions to maintain normal operations.

Parisky KM, Agosto Rivera JL, Donelson NC, Kotecha S, Griffith LC. Reorganization of Sleep by Temperature in Drosophila Requires Light, the Homeostat, and the Circadian Clock. Curr Biol. 2016.

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. 

Protected by Akismet
Blog with WordPress

Welcome Guest | Login (Brandeis Members Only)