MRSEC offers 2 one-week courses in Summer 2017

Brandeis’ MRSEC is offering two one-week courses in June 2017. “Introduction to Microfluidics Technology” and “Biomaterials: Kinesin Production for Beginners” are both hands-on laboratory courses with no prerequisites.

  • Introduction to Microfluidics Technology
    Date: June 19-23, 2017
    This course is intended for graduate students, post docs, faculty, and industrial scientists/engineers interested in utilizing microfluidic technology in their work, both in the physical and life sciences
  • Biomaterials: Kinesin Production for Beginners
    Date: June 26-30, 2017
    This course is intended for graduate students, postdocs, faculty, and industrial scientists/engineers interested in laboratory-scale expression and purification of kinesins, the biomolecular motors that power Brandeis MRSEC’s highly regarded active liquid crystals. The course is suitable for non-biologists who do not have access to any major specialized equipment at their home institution, since the goal of the course is to make protein production accessible to a wider variety of labs.

Register early (by March 1) for a $50 discount. Regular registration for both courses closes March 31, 2017.

Both courses are sponsored by the National Science Foundation’s Bioinspired Soft Materials Research Science and Engineering Center (MRSEC) at Brandeis.

The Benefits of Middle Age

Almost all our cells harbor a sensory organelle called the primary cilium, homologous to the better known flagella found in protists. Some of these cilia can beat and allow the cell to move (eg. in sperm), or move fluid (eg. cerebrospinal fluid) around them. However, other specialized cilia such as those found in photoreceptor cells and in our olfactory neurons function solely as sensory organelles, providing the primary site for signal reception and transduction. The vast majority of our somatic cells display a short and simple rod-like cilium that plays crucial roles during development and in adulthood. For instance, during development, they are essential for transducing critical secreted developmental signals such as Sonic hedgehog that is required for the elaboration of cell types in almost every tissue (eg. in brain, bones, muscles, skin). In adults, cilia are required for normal functioning of our kidneys, and primary cilia in hypothalamic neurons have been shown to regulate hunger and satiety.

Given their importance, it is not surprising that defects in cilia structure and function lead to a whole host of diseases ranging from severe developmental disorders and embryonic lethality to hydrocephalus (fluid accumulation in the brain), infertility, obesity, blindness, and polycystic kidney among others. Often these diseases manifest early in development resulting in prenatal death or severe disability, but milder ciliary dysfunction leads to disease phenotypes later in life.

Much is now known about how cilia are formed and how they function during development. However, surprisingly, how aging affects cilia, and possibly the severity of cilia-related diseases, is not well studied. A new study by postdocs Astrid Cornils and Ashish Maurya, and graduate student Lauren Tereshko from Piali Sengupta’s laboratory, and collaborators at University College Dublin and University of Iowa, begins to address this question using the microscopic roundworm C. elegans (pictured below). These worms display cilia on a set of sensory neurons; these cilia are built by mechanisms that are similar to those in other animals including in humans. Worms have a life span of about 2-3 weeks, thereby making the study of how aging affects cilia function quite feasible.

benefits-midage

They find that cilia structure is somewhat altered in extreme old age in control animals. However, unexpectedly, when they looked at animals carrying mutations that lead to human ciliary diseases, the severely defective cilia seen in larvae and young adults displayed a partial but significant recovery during middle-age, a period associated with declining reproductive function. They went on to show that the heat-shock response and the ubiquitin-proteasome system, two major pathways required for alleviating protein misfolding stress in aging and neurodegenerative diseases, are essential for this age-dependent cilia recovery in mutant animals. This restoration of cilia function is transient; cilia structure becomes defective again in extreme old age. These results suggest that increased function of protein quality control mechanisms during middle age can transiently suppress the effects of some mutations in cilia genes, and raise the possibility that these findings may help guide the design of therapeutic strategies to target specific ciliary diseases. Some things can improve with aging!

How different metals stick together

Editor: Tamara Hanna JEM: Esther RTP: Bryan Nolte

Cover artwork from Inorganic Chemistry featuring paper from the Thomas group

Metal-metal interactions are at the heart of some of the most interesting metal-catalyzed transformations and are found everywhere from Nature (metalloenzymes) to industrially important heterogeneous catalysis (surfaces, nanomaterials).  While textbooks have been written about metal-metal multiple bonds, surprising gaps in knowledge remain, including bonding between first row transition metals and bonding between different metals.  The Thomas group in the Brandeis Chemistry Department seeks to fill these gaps in knowledge through the systematic synthesis of heterobimetallic complexes featuring a wide range of different transition metals and developing a thorough understanding of the electronic structure and bonding of these novel compounds.

The latest issue of Inorganic Chemistry features cover artwork highlighting the recent paper from the Thomas laboratory titled “Exploring Trends in Metal–Metal Bonding, Spectroscopic Properties, and Conformational Flexibility in a Series of Heterobimetallic Ti/M and V/M Complexes (M = Fe, Co, Ni, and Cu).” The paper describes an extensive study of a series of Ti/M and V/M heterobimetallic complexes, where M is systematically varied across the periodic table from left to right (Fe, Co, Ni, Cu).  These complexes are classified as “early/late” heterobimetallic complexes because they feature one metal from the left half of the periodic table (“early”) and one metal from the right half of the periodic table (“late”).  The inherent differences between the properties of the two metals makes their metal-metal bonding quite polar and sensitive to a variety of different factors, but also poises these compounds for interesting reactivity because of the two electronically different metal sites presented. This latest installation from the Thomas group uncovers trends in metal-metal bond distance determined using X-ray crystallography, and uses a variety of spectroscopic (EPR, NMR, Mossbauer) and computational tools to probe the electronic structure of these compounds.  Most interestingly, these compounds are shown to be conformationally flexible, with ligand rearrangements occurring rapidly in solution and this ligand hemilability, which is ideal for facilitating reactivity, can be correlated directly with the strength of metal-metal interactions.

This paper was highly collaborative and its preparation involved researchers from both Brandeis and Harvard University. The synthesis and characterization of the new compounds were largely carried out by Bing Wu, a graduate student in the Thomas group, along with Chris Thomas herself. Matt Wilding, a recent Ph.D. graduate student from the Betley laboratory at Harvard University, assisted with the collection and interpretation of Mossbauer data and designed the cover artwork. Recent Ph.D. graduate Mark Bezpalko, of the Thomas/Foxman groups, and Bruce Foxman carried out all of the structural work in the Brandeis X-ray Diffraction Facility, and all of the computational studies were carried out by Bing Wu and Chris Thomas using the Brandeis high performance cluster.

Irving Epstein has been named AAAS Fellow

irving-epstein

In recognition of his contribution to the study of oscillating chemical reactions, Irving Epstein, the Henry F. Fischbach Professor of Chemistry, has been selected as a Fellow in the American Association for the Advancement of Science (AAAS).

Epstein, who in his 45 years at Brandeis has served as Provost and Dean of the Arts and Sciences, said he was honored to receive the award from the AAAS. “I’m delighted and grateful for the recognition,” he said. “It’s always nice to be appreciated by fellow scientists.”

 

Brandeis Receives Major Grant from the Mellon Foundation

Brandeis University has received a major grant to expand the LAPPS Grid Project that seamlessly connects open-source computer programs to quickly analyze huge amounts of language from diverse sources and genres.

James Pustejovsky

James Pustejovsky

Brandeis University has been awarded a two-year, $390,000 grant from the Andrew W. Mellon Foundation to lead an international collaboration to link the two major American and European infrastructures for the computational analysis of natural language. The resulting meta-framework has the potential to transform scholarship and development across multiple disciplines in the sciences, language and social sciences, and digital humanities by enabling scholars in Europe, the US, and Asia to work seamlessly across a massive range of software tools and data resources, developed separately by the American and European efforts. Led by James Pustejovsky, the TJX/ Feldberg Professor of Computer Science at Brandeis, the project team includes Nancy Ide (Vassar College), Erhard Hinrichs (University of Tübingen), and Jan Hajic (Charles University Prague).

The Language Applications (LAPPS) Grid Project—a collaborative, NSF-funded effort among Vassar, Brandeis, Carnegie Mellon University, and the Linguistic Data Consortium at the University of Pennsylvania—and the European Common Language Resources and Technology Infrastructure (CLARIN) are both frameworks (“grids”) that create and provide access to a broad range of computational resources for analyzing vast bodies of natural language data: digital language data collections, digital tools to work with them, and expertise for researchers to use them. Within each framework, members adhere to common standards and protocols, so that tools and data from different projects are “interoperable”: users can access, combine, and chain data from different repositories and tools from different sources to perform complex operations on a single platform with a single sign-on.

But the LAPPS Grid and CLARIN are not themselves interoperable. Researchers using data and tools in one framework cannot easily access or add data and tools from the other. LAPPS Grid users cannot access CLARIN’s multi-lingual services for digital humanities, social sciences, and language technology research and development, like Prague’s tools for search of oral history archives (developed to support their hosting the USC Shoah Archive), or Tübingen’s WebLicht services for data mining political and social science documents. CLARIN users don’t have access to the LAPPS Grid’s state-of-the-art tools for English and, through the LAPPS Grid’s federation with five Asian grids, to services providing a broad spectrum of capabilities for work in Asian languages. Scholars manually annotating a text corpus with CLARIN’s WebAnno (developed at TU-Darmstadt) would love to feed their work through iterative machine learning and evaluation facilities in the LAPPS Grid—but can’t.

The new Mellon Foundation funding will enable the project team to make the two grids interoperable on three levels:

  • Infrastructural: While the LAPPS Grid and CLARIN are both committed to open data and software, they do provide secure access to licensed resources, including the vast majority of the language data available over the web. The team will create a “trust network” between the two services, enabling single-authentication sign-on;
  • Technical: The LAPPS Grid and CLARIN have different underlying architectures and data exchange formats. The team will map these architectures and formats onto one another, enabling communication between the two frameworks over the web;
  • Semantic: To combine differently curated datasets, the data needs not only to share or be converted into a common format, but must also share a vocabulary for describing basic linguistic structures (a common language ontology) that tells computers how to combine the data into meaningful statements. The project team will extend the common exchange vocabulary developed by the LAPPS Grid to the web services of both frameworks and implement a set of conversion services.

The project will dramatically extend the power and reach of both the European and American frameworks and put their combined resources at the direct disposal of scholars from a broad range of fields in the humanities and social sciences, without requiring them to be computer programmers. “It will effectively create an ‘internet of language applications’ for the everyday computer user,” explained Dr. Pustejovsky. “We’re going to give every scholar access to a toolkit that’s now only available to the largest corporations.”

 

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!

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.

Stx.key

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

REU-students-interview-600

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.

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