2nd Boston Symposium of Encoded Library Platforms to be held Aug. 4

BSELP imageThe Brandeis Chemistry Department, together with GlaxoSmithKline and Pharmaron, is hosting the 2nd Boston Symposium of Encoded Library Platforms on August 4th in the Shapiro Theater. This symposium will feature 8 speakers from industry and academic labs, covering the newest developments in the technology of encoded small molecule libraries and related topics.

For several decades, major efforts have gone into discovering drug leads by high-throughput screening, in which “libraries” of thousands to millions of random compounds are tested in a highly repetitive fashion for biological activity, such as the ability to inhibit an enzyme. A new and elegant alternative to this process is the use of encoded libraries, in which each random molecule within the library bears a “tag” of DNA with a unique sequence. Libraries containing hundreds of millions of DNA-tagged compounds can be incubated with a target protein in a single tube, and those which bind to the target can be identified by high-throughput sequencing of the DNA barcodes in the protein-bound fraction. This approach has gained great popularity in the last few years, and is just this week the cover story of Chemical & Engineering News.

Two Brandeis Professors Receive 2017 Simons Fellowships, part II

Spectral Flow

Spectral Flow (full caption below)

Two Brandeis professors have been awarded highly prestigious and competitive Simons Fellowships for 2017. Daniel Ruberman received a 2017 Simons Fellowship in Mathematics. Matthew Headrick was awarded a 2017 Simons Fellowship in Theoretical Physics. This is the second of two articles where each recipient describes their award-winning research.

Daniel Ruberman’s research asks “What is the large-scale structure of our world?” Einstein’s unification of physical space and time tells us that the universe is fundamentally 4-dimensional. Paradoxically, the large-scale structure, or topology, of 4-dimensional spaces, is much less understood than the topology in other dimensions. Surfaces (2-dimensional spaces) are completely classified, and the study of 3-dimensional spaces is largely dominated by geometry. In contrast, problems about spaces of dimension greater than 4 are translated, using the technique called surgery theory, into the abstract questions of algebra.

Ruberman will work on several projects studying the large-scale topology of 4-dimensional spaces. His work combines geometric techniques with the study of partial differential equations arising in physics. One major project, with Nikolai Saveliev (Miami) is to test a prediction of the high-dimensional surgery theory, that there should be `exotic’ manifolds that resemble a product of a circle and a 3-dimensional sphere. The proposed method, which would show that this prediction is incorrect, is to compare numerical invariants derived from the solutions to the Yang-Mills and Seiberg-Witten equations, by embedding both in a more complicated master equation. The study of the Seiberg-Witten invariants is complicated by their instability with respect to varying geometric parameters in the theory. A key step in their analysis is the introduction of the notion of end-periodic spectral flow, which compensates for that instability, as illustrated below.

Other projects for the year will apply techniques from 4-dimensional topology to classical problems of combinatorics and geometry about configurations of lines in projective space. In recent years, combinatorial methods have been used to decide if a specified incidence relation between certain objects (“lines”) and other objects (“points”) can be realized by actual points and lines in a projective plane. For the real and complex fields, one can weaken the condition to look for topologically embedded lines (circles in the real case, spheres in the complex case) that meet according to a specified incidence relation. Ruberman’s work with Laura Starkston (Stanford) gives new topological restrictions on the realization of configurations of spheres in the complex projective plane.

Caption: Solutions to the Seiberg-Witten equations of quantum field theory provide topological information about 4-dimensional spaces. However, the set of solutions, or moduli space, can undergo a phase transition as a parameter T is varied, making those solutions hard to count. This figure illustrates a key calculation: the phase transition is equal to the end-periodic spectral flow, a new concept introduced in work of Mrowka-Ruberman-Saveliev. In the figure, the spectral set, illustrated by the red curves, evolves with the parameter T. Every time the spectral set crosses the cylinder, the moduli space changes, gaining or losing points according to the direction of the crossing.

Learning to see

How do we learn to see? Proper visual experience during the first weeks and months of life is critical for the proper development of the visual system. But how does experience modify neural circuits so that they exhibit the proper responses to visual stimuli? Knowledge of the mechanisms by which the brain is constructed early in development should inspire new therapies for repairing the brain if it develops improperly or is damaged by disease or injury.

At the present time, it is not possible to directly view all or even most connections within a living neural circuit. Therefore, neuroscientists often build computational models to study how these circuits may be constructed and how they may change with experience. A good model allows scientists to understand how these circuits may work in principle, and offers testable predictions that can be examined in the living animal to either support or refute the model.

Undergraduate Ian Christie ’16 was interested in understanding how neural circuits in the ferret visual system become selective to visual motion. At the time of eye opening, neurons in ferret visual cortex respond to an object moving in either of two opposite directions. With about a week of visual experience, each neuron develops a preference for only one of these directions, and greatly reduces its responses to the opposite direction.

Previous models of this process posited that the primary source of the change was in the organization and pattern of inputs to the cortex. But, recent experiments from the Van Hooser lab (Roy/Osik/Ritter et al., 2016) showed that stimulating the cortex by itself was sufficient to cause the development of motion selectivity, which suggests that some changes within the cortex itself must be underlying the increase in selectivity, at least in part. Further, other experiments in the lab of former Brandeis postdoc Arianna Maffei (Griffen et al., 2012) have shown that the cortex becomes less excitable to focal stimulation over the first weeks after eye opening.

Ian constructed families of computational models that could account for both of these observations. In the model, columns of neurons in the cortex already receive input that is slightly selective for motion in one of two opposite directions, but the connections between these cortical columns are so strong that both columns respond to both directions. However, the activity that is caused by simulated visual experience activates synaptic plasticity mechanisms in the model, that served to greatly reduce the strength of these connections between the columns, allowing motion selectivity to emerge in the cortical columns. The project was supervised by faculty members Paul Miller and Stephen Van Hooser, and the results were published in Journal of Neurophysiology (Christie et al., 2017).

Future experiments will now look for evidence of weaker connectivity between cortical neurons with visual experience.

This work was supported by the “Undergraduate and Graduate Training in Computational Neuroscience” grant to Brandeis University from NIH, and by the National Eye Institute grant EY022122. It also used the Brandeis University High Performance Computing Cluster.

Physics department mourns passing of Professor Emeritus Sam Schweber

Sam SchweberSam Schweber, Professor Emeritus of Physics, died May 14th at the age of 89. A theoretical physicist and historian of science, Sam was among that first generation of Brandeis faculty whose genius turned a fledgling institution into a university of the first rank. He published his first book in 1956, when not yet thirty, and his last in 2012, in his mid-eighties. His was an extraordinary life and career.

Sam was born in Strasbourg and came to this country at the age of 14. Like many immigrants and children of immigrants, he attended college at City College of New York, and he then went on to earn an M.S. from the University of Pennsylvania and a Ph.D. from Princeton. A postdoctoral fellowship at Cornell gave him the special opportunity to work under Hans Bethe (whose biography he wrote, many years later). Sam came to Brandeis in 1955 as associate professor of physics and quickly became involved in building the young department. In 1957, the Physics Department started a graduate program, and the following year it established, at Sam’s initiative, a summer institute in theoretical physics, bringing to campus leading physicists as well as selected graduate students and postdocs, for weeks of seminars and colloquia. The institute ran annually for fifteen years, until the federal funding ceased.

The young Sam Schweber had clearly impressed Hans Bethe. In 1955 he co-authored with Bethe (and a third physicist) the two-volume Mesons and Fields, and in 1960, the same three authors published Quantum Theory of Fields. A year after that, in his foreword to Sam’s new book, An Introduction to Relativistic Quantum Field Theory, Bethe observed, “It is always astonishing to see one’s children grow up, and to find that they can do things which their parents no longer fully understand.” This book remains in print five decades after its initial publication.

Sam continued to conduct research and publish in the field of quantum field theory, while also playing an integral part in the growth of Brandeis University. His scholarly interests then started to shift. Volunteering to teach a course on how probability entered the sciences, he became fascinated with the history of science and chose to spend his next sabbatical in the History of Science Department at Harvard. In the third decade of his career, Sam became a historian of science. He joined our interdepartmental program in History of Ideas, and in 1982 was appointed to the Koret Chair in the History of Ideas.

Sam became equally eminent in his new field, publishing a series of significant books and helping to found and then lead the Dibner Institute for the History of Science and Technology at MIT. Sam brought to his writing not only rigorous historical research and a deep understanding of science, but also a strong interest in the human dimension and social consequences of scientific research and discovery. Among his many books were Einstein and Oppenheimer: The Meaning of Genius, In the Shadow of the Bomb: Oppenheimer, Bethe and the Moral Responsibility of the Scientist, and Nuclear Forces: The Making of the Physicist Hans Bethe. Describing another of Sam’s books, Freeman Dyson wrote that “he has produced a lively and readable narrative history, with a lightness of touch than can come only to one who is absolute master of his subject.”

Sam continued to be an active scholar and author after his retirement from Brandeis in 2003. In 2011, he won the Abraham Pais Prize for History of Physics. The citation spoke of “his sophisticated, technically masterful historical studies” and his “broadly insightful biographical writing on several of the most influential physicists of the 20th century.” Sam was a Fellow of the American Physical Society, the American Association for the Advancement of Science, and the American Academy of Arts and Sciences. A further measure of his stature and influence came in the past few days, from the Max-Planck-Institut fur Wissenschaftsgeschichte: “It is with deep regret that we announce the passing on May 14, 2017 of the distinguished historian of science, Professor Sam S. Schweber. Sam was a dear colleague and mentor of many at the Institute and will be sorely missed by all those who had the great fortune and pleasure of knowing him.”

That sentiment will surely be echoed by the many former Brandeis colleagues and students who greatly admired Sam and learned from him.

Brandeis’ Pioneering Science Posse Program

Photo: Mike Lovett

Samia Tamazi ’20

BrandeisNow has posted an article about the history and accomplishments of the Brandeis’ Science Posse program. Read the following excerpt or the entire article:

In June, Macareno and his posse, all Class of 2020, get off Amtrak’s Acela Express train and take a shuttle bus to Brandeis for science boot camp. On the first day, they gather in a classroom in the Abelson physics building […]

(Melissa) Kosinski-Collins, who earned a PhD at MIT, tells them college science is profoundly different from high-school science. With equal parts candor and caring, she sets high expectations, describing the intense workload. The students know that they will be held to lofty standards and that she will support them.

Later in the day, they gather around a long lab table in the Shapiro Science Center, in an area Kosinski-Collins calls Hufflepuff — a nod to one of the houses at Harry Potter’s Hogwarts School. An array of equipment is scattered before them — pipettes, balances, bottles of acetic acid (vinegar) and sodium bicarbonate (baking soda). There are also aluminum foil, Kimwipes, Scotch tape and Ziploc bags.

The students’ assignment is to build an air bag. When acetic acid combines with sodium bicarbonate, they produce carbon dioxide. The students must figure out how much of each chemical to add to fully inflate a quart-size Ziploc bag. But they also have to protect an egg placed inside the bag. This is where the foil, tape and extra bags come in. Along with the cushion of air, these items can be used to keep the egg from cracking when they drop the bag from the Science Center steps, about 15 feet above the ground.

There’s an important catch. Several months earlier, at a meeting in New York, the students got the same assignment. They also completed lab reports describing the quantities of chemicals they used and how they arranged the materials inside the bag to protect the egg. These lab reports are now handed out to different students. They have 10 minutes to repeat the earlier experiment using the reports as a guide […]

Read more at BrandeisNow

Pump without pumps

By Kun-Ta Wu, Ph.D.

Pumping water through a pipe solves the need to provide water in every house. By turning on faucets, we retrieve water at home without needing to carry it from a reservoir with buckets. However, driving water through a pipe requires external pressure; such pressure increases linearly with pipe length. Longer pipes need to be more rigid for sustaining proportionally-increased pressure, preventing pipes from exploding. Hence, transporting fluids through pipes has been a challenging problem for physics as well as engineering communities.

To overcome such a problem, Postdoctoral Associate Kun-Ta Wu and colleagues from the Dogic and Fraden labs, and Brandeis MRSEC doped water with 0.1% v/v active matter. The active matter mainly consisted of kinesin-driven microtubules. These microtubules were extracted from cow brain tissues. In cells, microtubules play an important role in cell activity, such as cell division and nutrient transport. The activity originates from kinesin molecular motors walking along microtubules. In cargo transport, microtubules are like rail tracks; kinesin motors are like trains. When these tracks and trains are doped in water, their motion drives surrounding fluids, generating vortices. The vortices only circulate locally; there is no global net flow.

Wu-Pump without Pumps

Figure: Increasing the height of the annulus induces a transition from locally turbulent to globally coherent flows of a confined active isotropic fluid. The left and right half-plane of each annulus illustrate the instantaneous and time-averaged flow and vorticity map of the self-organized flows. The transition to coherent flows is an intrinsically 3D phenomenon that is controlled by the aspect ratio of the channel cross section and vanishes for channels that are either too shallow or too thin. Adapted from Wu et al. Science 355, eaal1979 (2017).

[Read more…]

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