Waltham Teachers Meet with Brandeis Scientists

Brandeis scientists & Waltham teachers

On Tuesday, November 7th, 32 science teachers from Waltham Public Middle and High Schools visited the Brandeis science labs as part of the Third Annual Brandeis Scientists in the Classroom Workshop. The workshop is designed to be an opportunity to connect middle and high school science teachers with Brandeis scientists. The teachers were grouped and matched with 14 Brandeis graduate students, postdocs and faculty who shared their Brandeis science research directly with the teachers to help them understand what we do, so they can better integrate science into their classroom lessons.

This event was an extension of an ongoing partnership between Brandeis and Waltham High School and was sponsored by the Brandeis MRSEC. The Waltham school district has a high percentage of students from backgrounds underrepresented in the sciences. Brandeis offers several on-going programs with Waltham teachers and students in an effort to broaden their participation in STEM.

Eisenbud Lectures in Mathematics and Physics set for November 27-29, 2017

The Departments of Physics and Mathematics at Brandeis University are incredibly excited to announce that this year’s Eisenbud Lectures in Mathematics and Physics will be given Prof. James P. Sethna, a theoretical physicist whose work has often carved out new directions in condensed matter physics, in its broadest interpretation.

The Eisenbud Lectures are the result of a bequest by Leonard and Ruth-Jean Eisenbud, and this year marks the 100th anniversary of Leonard Eisenbud’s birth. Leonard Eisenbud was a mathematical physicist at SUNY-Stony Brook; upon his retirement he moved to the Boston area, as his son David was a member of the Mathematics faculty at Brandeis, and was given a desk here. The bequest is for an annual lecture series by physicists and mathematicians working on the boundary between the first two fields.

Prof. Sethna has tackled traditional and highly non-traditional topics in Physics. The title of one of his recent talks is “The Statistical Mechanics of Zombies”!. “Mosh Pit Dynamics at Heavy Metal Concerts” is another example where Jim uses the tools of statistical mechanics to understand a social phenomenon. Jim is a fascinating speaker, and these lectures promise to be enlightening and entertaining in equal measure. His playful enthusiasm for science is certain to draw you in. So, try not to miss this year’s series of three Eisenbud Lectures.

The first lecture on Monday, November 27 will be on “Sloppy models, Differential geometry, and How Science Works”, and is intended for a general science audience. This lecture will be held in Gerstenzang 121 at 4 PM. The second lecture on Tuesday, November 28 will be a colloquium-style lecture entitled “Crackling Noise” and will take place in Abelson 131 at 4 PM. The final lecture, “Normal form for renormalization groups: The framework for the logs” will be delivered at 10 AM on Wednesday, November 29 in Abelson 333.

Refreshments will be served 15 minutes prior to each talk. There will be a reception in Abelson 333 following Tuesday’s talk.

Additional information is available on the lecture’s website.

We hope to see you all at what promises to be an exciting series of talks!

Rodal lab find surprising new link between inflammation and Lowe Syndrome

Could a disease with symptoms in the brain, eyes, and kidneys actually be caused by problems with immune cells? A team of scientists from the Rodal Lab, co-first authored by Steven Del Signore and Sarah Biber and including three Brandeis undergraduates (Katy Lehmann ‘16, Stephanie Heimler ‘17, and Ben Rosenfeld ’18), think this just might be the case with Lowe Syndrome, in a new paper published Oct 13th in PLOS Genetics.

Patients with Lowe Syndrome suffer from kidney failure, congenital cataracts, and several neurological problems including intellectual disability and seizures. Scientists have known for some time that the disease is caused by mutations in a gene called OCRL, but remain unsure how its loss causes such a diverse array of symptoms. A big problem has been that OCRL appears to do many different jobs inside cells, including controlling how they divide, how they sense their surroundings, and how they store and transport materials inside small packages called endosomes.

Fly immune cells showing the tracks of moving endosomes. Single tracks represent the path of individual endosomes over time.

To try to solve this mystery, a team of researchers from the Rodal lab used the fruit fly, which has its own version of the OCRL gene and allowed the investigators to perform powerful genetic experiments to figure out precisely what OCRL is doing, and where. To do this, the group created a fly missing its OCRL gene. They were surprised to find that, rather than eye or neurological defects, loss of OCRL hyper-activated cells of the innate immune system. The innate immune system is the first line of defense against infection in humans (and the only defense in fruit flies), when cells release inflammatory signals that mobilize specialized cells to attack invading pathogens.

The team determined that OCRL is required in one of these specialized immune cells in the fly, and that the immune-cell activation was caused by problems in a particular step of intracellular transport. Every cell of the body has its own postal service, which is used to pack and ship signals that tell the cell or its neighbors to grow, divide, or jump into action (see movie here to watch endosomes moving inside living fly immune cells). The OCRL mutant immune cells had a problem in a key step that controls whether signals get thrown in the trash or shipped outside the cell, and this caused the immune activation.

How do these findings relate to Lowe Syndrome? The authors think these results suggest a possible cause for the seizures that patients experience. When similar immune-like cells in the brain release excessive inflammatory signals, it can cause several forms of epilepsy. Further, OCRL has been linked to at least one mouse model of epilepsy. Going forward, the researchers will try to identify which immune signals are responsible, and how these findings translate to human cells.

Del Signore SJ (*), Biber SA (*), Lehmann KS, Heimler SR, Rosenfeld BH, Eskin TL, Sweeney ST, Rodal AA. dOCRL maintains immune cell quiescence by regulating endosomal traffic. Plos Genet. 2017;13(10):e1007052.



Ivanovic Receives 2017 NIH Director’s New Innovator Award

photo: Mike Lovett

Assistant Professor of Biochemistry Tijana Ivanovic has received a 2017 NIH Director’s New Innovator Award. This award is part of the NIH’s High-Risk, High-Reward Research program, designed to fund early career investigators who propose innovative and potentially transformative projects. Ivanovic will receive $1,500,000 in direct costs over five years to spearhead a research program aimed at comprehensively characterizing molecular changes in the viral cell-entry protein hemagglutinin (HA) that define pandemic influenza viruses. With the generated insights, Ivanovic hopes to ultimately be in a position to predict the pandemic potential of influenza viruses circulating in nature.

HA densely covers the influenza virion surface, where it allows the virus to both recognize and penetrate (fuse with) the cells of its host. HA is also a key target of neutralizing antibodies that protect us from influenza infection. An influenza pandemic is characterized by the adaptation of a new HA subtype to cell entry into human cells (of what was originally an avian virus). Without the pre-existing immunity to protect us, the virus quickly spreads around the globe. During pandemic adaptation, both HA functions in target-cell recognition and membrane fusion undergo key molecular changes. Ivanovic will use a custom-built Total Internal Reflection Fluorescence Microscope (TIRFM) to visualize, in real time, individual virus particles as they engage and fuse with target cell membranes. This system will allow her to obtain large-scale quantitative information about distinct HA functions at an unprecedented level of detail. She will compare avian viruses with their evolutionary offspring that infected humans, including past pandemic strains. She hopes to develop models for predicting which viruses will lead to a major flu outbreak.

Ivanovic obtained a PhD in virology from Harvard University and carried out postdoctoral research with Stephen Harrison in molecular biophysics. She integrates these diverse backgrounds in her laboratory, where members are trained across these two and other synergistic areas (such as laser microscope optics, and analytical and computational modeling). The funds from the New Innovator award have created new opportunities for hiring, and the lab is actively recruiting postdocs, PhD students (from the Biochemistry and Biophysics, Molecular and Cell Biology, and Physics graduate programs) and undergraduate researchers to undertake this ambitious program.

Titia de Lange to receive 47th Rosenstiel Award

Professor Titia de Lange

The 47th Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research has been awarded to Professor Titia de Lange of Rockefeller University for her studies on the protection of chromosome ends (telomeres) from degradation and rearrangement. Professor de Lange will receive the award on April 12, 2018 at Brandeis University where de Lange will present a public lecture.

Dr. de Lange’s laboratory identified and characterized the roles of proteins that compose the shelterin complex, which binds specifically to the special telomeric DNA sequences and maintains the stability of these ends.  Dr. de Lange’s work has shown that the shelterin complex and the unusual telomere-loop structure of telomere DNA prevent these ends from being detected as broken chromosome ends and thus protect telomeres from being degraded and rearranged as are the ends at chromosome breaks.  De Lange’s work has further shown that disabling different components of shelterin triggers different cellular alarms designed to detect broken and degraded DNA ends and leads to lethal chromosome rearrangements such as the fusion of chromosomes.  In addition, her lab has gained critical insights into the mechanisms of cellular response to the presence of DNA damage and recently has defined processes that lead to massive chromosome rearrangements (chromothripsis) associated with many human cancers.

She is the Leon Hess Professor and director of the Anderson Center for Cancer Research at Rockefeller University, as well as an American Cancer Society Research Professor.  Her honors include: the Life Sciences Breakthrough Prize, the Rosalind E. Franklin Award from the National Cancer Institute, the Vilcek Prize in Biomedical Sciences, election as a foreign member of the US National Academy of Sciences and as Fellow of the American Academy of Arts and Sciences.

The Rosenstiel Award has had a distinguished record of identifying and honoring pioneering scientists who subsequently have been honored with the Lasker and Nobel Prizes.  Professor de Lange joins a long list of past awardees.

Stanley Deser’s Influence on the 2017 Nobel Prize for Physics

Written by Albion Lawrence

Deser, Arnowitt, & Miser

Bornholm 1959
From the left, Richard Arnowitt, Charles Misner and Stanley Deser

Today’s Physics Nobel Prize to Rai Weiss, Kip Thorne, and Barry Barish for the detection by the LIGO experiment of gravitational waves is a well-deserved recognition of a remarkable achievement through perseverance. However, it is the nature of prizes such as the Nobel that they obscure the important efforts and insights of many scientists across space and time that lead to the result in question.

Stanley DeserThe extraction of a gravitational wave signal from the output of the LIGO detector requires understanding in advance what signals can be produced; these are based on numerical simulations of astrophysical events which provide templates that a signal must match.

This is possible due to the seminal work of Brandeis emeritus faculty Stanley Deser, with his colleagues Richard Arnowitt and Charles Misner, who developed the mathematical framework known as the ADM formalism, to treat general relativity as a Hamiltonian system; with this, the evolution in time of the gravitational field can be computed from initial conditions.

In addition, Stanley was instrumental in the LIGO experiment being funded in the first place. The story is best told by him in his inimitable style (here quoted from an email, and lightly expurgated):

“Marcel Bardon, then [director] of NSF physics, made me an offer I’d better not refuse. I was nominated to some advisory committee in order to plead for LIGO in front of my betters, who would then go to Congress, if convinced. Those were dark days for waves, experimentally; we (ADM) of course knew the Lord was not evil, but 3 suns’ worth we did not expect!….It worked quite well, and was duly made a line item.”

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