Division of Science Hosts the 2016 Undergraduate Science Symposium

Written by Jena Pitman-Leung.

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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!

68th New England Complex Fluids Workshop, September 23, 2016

The 68th New England Complex Fluids Workshop will be held 9:00 am – 4:00 pm Friday, September 23, 2016 at the Shapiro Campus Center on Brandeis University. NECFW68 will feature two research talks, two soundbite sessions and one panel of scientists who are thriving after leaving academia for industry.

Online registration for the meeting is required, but thanks to the NSF Brandeis MRSEC, it is free. However, please register by 8 am, September 20 so we can order enough food for you.

NECFW‘s goal is to encourage collaboration among researchers from industry and academe in the New England area studying Soft Condensed Matter. We hold one day workshops four times a year which offer the opportunity for discussion and exchange of ideas between students, post-docs, and professionals. An additional objective is to further the career development of students and post-docs by introducing them to the local academic and industrial research community.

Please register at the complex fluids website: http://www.complexfluids.org. If you would like to present a 4:00 minute soundbite, submit your talk title and abstract when you register for the meeting. Soundbites are restricted to the first 25 submissions. Additional information such as maps, directions, schedule and a list of registered attendees is available at the website as well.

This year will feature an Industrial Panel to tell tales of life after academia. Entrepreneurs and industrial scientists will describe their pathway to creating companies, discuss which qualities they seek in applicants and answer the following questions. What kind of training and education do industrial labs seek in job applicants? What scientific and other knowledge should applicants possess? experience? skills? creativity? business knowledge? What should the universities do to better prepare students for a career in industry? What do the panel members wish they did differently in college to better prepare themselves for industry? What should students / postdocs be doing now to prepare for an industrial career? How can students find an internship? How should students build a network of contacts to help them find a job? How does research done in industry compare to that done in universities? What (if any) is the relevancy of research being done at universities to entrepreneurs, industrial scientists and managers?

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.

SciFest VI recap and stats

photo credit: Mike Lovett

photo credit: Mike Lovett

The Brandeis University Division of Science held its annual undergraduate research poster session SciFest VI on August 4, 2016, as a record number of student researchers presented posters with the results of their summer’s (or last year’s) worth of independent research. We had a great audience of grad students, postdocs, faculty, proud parents, and senior administrators.

More pictures and abstract books are available at the SciFest site.

SciFest VI by numbers

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.

Amy Lee Joins Biology Faculty

On August 1, Amy Lee joined the Biology department as an Assistant Professor. Previously, Amy was an American Cancer Society Postdoctoral Scholar in Jamie Cate’s lab at University of California, Berkeley. She received her Ph.D. in Virology from Harvard University in Sean Whelan’s lab and her Bachelors of Science in Biology from Massachusetts Institute of Technology.

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eIF3d structure, see Figure 2 at http://rdcu.be/jzDD

Amy’s research focuses on understanding how gene regulation shapes cell growth and differentiation, and how dysregulation leads to human diseases like carcinogenesis and neurodegeneration. She is interested in discovering new mechanisms of mRNA translation initiation and novel functions of RNA-binding proteins and eukaryotic translation factors. Her research combines genome-wide and computational approaches together with molecular genetics, cell biology, biochemistry, and structural biology techniques.

Amy recently published a paper in Nature together with the Jamie Cate, Jennifer Doudna, and Philip Kranzusch describing the discovery of a new translation pathway that controls the production of proteins critical to regulating the growth and proliferation of cells. Cancer is characterized by uncontrolled cell growth, which means the protein production machinery goes into overdrive to provide the building materials and control systems for new cells. Hence, biologists for decades have studied the proteins that control how genes are transcribed into mRNA and how the mRNA is read and translated into a functioning protein. One key insight more than 40 years ago was that a so-called initiation protein must bind to a chemical handle on the end of each mRNA to start it through the protein manufacturing plant, the ribosome. Until now, this initiation protein was thought to be eIF4E (eukaryotic initiation factor 4E) for all mRNAs.

Amy and her colleagues discovered that for a certain specialized subset of mRNAs – most of which have been linked somehow to cancer – initiation is triggered by a different protein, called eIF3d. The finding was a surprise because the protein is part of an assembly of 13 proteins called eIF3 -eukaryotic initiation factor 3 – that has been known and studied for nearly 50 years, and no one suspected its undercover role in the cell. This may be because eIF3’s ability to selectively control mRNA translation is turned on only when it binds to the set of specialized mRNAs. Binding between eIF3 and these mRNAs opens up a pocket in eIF3d that then latches onto the end-cap of mRNA to trigger the translation process. Subsequent X-ray crystallography of eIF3d revealed the structural rearrangements that must occur when eIF3 binds to the mRNA tag and which open up the cap-binding pocket. eIF3d thus presents a promising new drug target in cancer, as a drug blocking this binding protein could shut off translation of only the growth-promoting proteins and not other life-critical proteins inside the cell.

Lee AS, Kranzusch PJ, Doudna JA, Cate JH. eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation. Nature. 2016.

 

REU Students Arrive for 2016 Summer Research

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Amber Jones and Susan Okrah

Alongside the more than 100 Brandeis science undergrads doing research this summer, there are 19 students who are participating in our Research Experiences for Undergraduates (REU) programs. Some students are from Brandeis, but most call universities in Kansas, Virginia, Pennsylvania, New Jersey their academic homes. Eight students are from Hampton University as part of the Partnership for Research and Education in Materials (PREM) initiative between Hampton and Brandeis. The two universities are focused on fostering interest in research science in under-represented groups of undergraduates.

The two independent REU programs were each created 6 years ago with funding from the National Science Foundation (NSF) with a goal of providing a 10-week period of intensive lab research experience to rising sophomores and juniors interested in scientific careers. Professor Susan Lovett is the director of the Cell and Molecular Visualization REU and Dr. Anique Olivier-Mason is the director of the Material Research Science and Engineering Center (MRSEC) REU.

The online application process required each student to submit a transcript, two letters of recommendation and write two essays describing their research experience (if any) and their academic and research goals. This year, 8 students are participating in the MRSEC site; 11 students are working in the Biology-based Cell and Molecular Visualization REU.

Amber Jones, who is going to be a junior at Hampton University this fall, is working in the Avi Rodal lab where she is researching how proteins can be taken on and off of cell membranes. From here, she is hoping to target specific proteins that will ultimately aid in disease research.

Amber has worked in a lab before, but believes nothing could have prepared her for her experience at Brandeis. Her REU lab work has been very involved, but she wasn’t expecting the ups and downs that are a part of lab research. The graduate students and other lab members have been supportive. She has been told “it’s okay; it’s science!”

Returning REU student, Alex Cuadros is working in the Liz Hedstrom lab, says he can go to Cell and Molecular Visualization REU coordinators Cara Pina and Laura Laranjo for assistance. They “have more experience in the lab and they tell me that things don’t always work for them. They say that ‘it’s just part of the science’.”

Nicholas Martinez, who is working in Timothy Street’s lab said, “The biggest challenge I have encountered this summer with my research is being able to do cope with disappointment. Since I am working on a defined timetable and my time here at Brandeis is limited, I want to make as much progress as possible with my research.”

Susan Okrah is working in the Seth Fraden lab this summer. She believes this experience is different from a Chemistry class at Hampton University where you are given an experiment and the results are known. In the REU program, students are given a project that is a subset of their lab’s research. Unlike school, the outcome of their research is unknown. Susan said, “We are given a direction and told to see if it works.”

Alex said that in class he has learned how to do experiments, but at Brandeis he is “doing something that has not been done before so there’s no right method.” It’s also helpful to be able to ask advice about how to approach his research and “Then you go back and you figure out how to do it. You are forced to think independently.”

During the academic year, Alex works in a Biochemistry lab at UMass Amherst. He landed the job last fall as a direct result of his 2015 REU research. How did he get the job in a very competitive environment on the large UMass campus? He presented the poster that he prepared for SciFest 2015.

The most valuable lesson learned this summer? “Resilience” said Amber. Learning to cope with the changing tides of research is important. As Susan said, “people don’t really understand what goes into research until they’re here.”

Part of the REU program involves attending journal clubs and lab meetings, but the most valuable experience of this program is simply being in a lab. Both Amber and Susan agree that anyone thinking about a career in research should go through an intensive research experience such as this. Jones noted, “I wasn’t really expecting to get this type of understanding. I really appreciate that now that I’m here.”

Both Nicholas and Alex ultimately would like to attend graduate school. For Nicholas, “being able to participate in the Cell and Molecular Visualization REU program at Brandeis has been a great opportunity for me to diversify my knowledge and skill set in scientific research prior to applying for graduate school next year. This It has been a great way for me to gain experience in a new area of research that I am interested in and to become part of a different scientific community.”

The REU students are hard at work wrapping up their research and preparing their posters for the SciFest 2016 poster session that is scheduled for Thursday, August 4.

Celebrating Chris Miller at Christravaganza Millerpalooza

Since its founding at Brandeis in 1976, Chris Miller’s lab has been home to 25 graduate students and 35 postdocs. Many of them, together with friends and colleagues from around the world, came together on July 8 and 9 for a two day symposium celebrating Chris’ 70th birthday.

For four decades Miller has used electrophysiological methods to study single ion channels. Ion channels are proteins that open and close, selectively allowing specific ions to cross cell membranes, for example to drive muscle contraction or nerve cell signaling. The selective transport of ions across membranes is a fundamental feature of cells.

Miller began studying channels selective for potassium ions, and then in 1978 discovered a chloride selective channel, from Torpedo, the first member of the important CLC chloride channels whose malfunction is implicated in a variety of diseases. (Its name comes from the electric ray Torpedo californica from which the channel was first isolated.) Chris discovered the unusual “double barreled” architecture of the CLC family of ion channels. The lab continues to work on related proteins, including Cl/H+ exchange-transporters.

Miller’s lab has followed clues in recent years to find additional novel channels to study, including bacterial proteins involved in acid resistance and most recently channels that are selective for fluoride. Chris has been a Howard Hughes Medical Institute investigator since 1989 and in 2007 he was elected to the US National Academy of Sciences.

Rod MacKinnon ’78 was Chris’ very first student while he was an undergraduate at Brandeis. After medical school, Rod came back to Chris’ lab as a postdoc, and together they investigated the mechanism of calcium activated potassium ion channels. Later, at Rockefeller University, Rod used high resolution x-ray diffraction to determine the complete molecular structure of the proteins that form the channel. For this he was awarded the Nobel Prize for Chemistry in 2003. The structure confirmed a cartoon picture of how the potassium channel works that Chris, with postdoctoral fellows MacKinnon and Jaques Neyton, had developed ten years earlier.

Chris’ wife, Brandeis Professor of Russian and Comparative Literature Robin Feuer Miller, and their three daughters were in attendance. Lulu Miller (who is also co-host of the NPR program Invisibilia) introduced her father for the final talk of the symposium.

The editors thank Dan Oprian for help with this article. The photographs were taken by Heratch Ekmekjian.

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