Using computer simulations to model bacterial microcompartment assembly

21 06 2016

Bacterial microcompartments are protein shells found in bacteria that surround enzymes and other chemicals required for certain biological reactions.  For example, the carboxysome is a type of microcompartment that enables bacteria to convert the products of photosynthesis into sugars (thus taking carbon out of the atmosphere).  During the formation of a microcompartment, the outer protein shell assembles around hundreds of enzymes and chemicals required for the reaction.  Because the intermediates in this assembly process are small and short-lived, it is hard to study in detail using experiments. It is therefore useful to develop computational models that can help explain how proteins collect the necessary cargo, and then assemble into an ordered shell with the cargo on the inside.  The videos in this post show some examples of computer simulations of a model for bacterial microcompartment assembly, with each video corresponding to a different set of parameters that control the strengths of interactions among the proteins and cargo.

The study is described in the research article “Many-molecule encapsulation by an icosahedral shell” by Jason Perlmutter, Farzaneh Mohajerani, and Michael Hagan in eLife (eLife 2016;10.7554/eLife.14078).

Video 1: Multistep assembly of a microcompartment encapsulating hundreds of molecules (I) video1
Video 2: Multistep assembly of a microcompartment encapsulating hundreds of molecules (II)  video2
Video 3: Assembly of a microcompartment and encapsulation of hundreds of diffuse cargo molecules  video3

Simons Foundation funds Brandeis Math, Physics collaborations

3 05 2016

In 2014, the Simons Foundation, one of the world’s largest and most prominent basic science philanthropies, launched an unprecedented program to fund multi-year, international research collaborations in mathematics and theoretical physics. These are $10M grants over four years, renewable, that aim to drive progress on fundamental scientific questions of major importance in mathematics, theoretical physics, and theoretical computer science. There were 82 proposals in this first round. In September 2015, two were funded. Both involve Brandeis.

Matthew Headrick (Physics) is deputy director of the Simons Collaboration It from Qubit, which involves 16 faculty members at 15 institutions in six countries. This project is trying from multiple angles to bring together physics and quantum information theory, and show how some fundamental physical phenomena (spacetime, black holes etc.) emerge from the very nature of quantum information. Fundamental physics and quantum information theory remain distinct disciplines and communities, separated by significant barriers to communication and collaboration. “It from Qubit” is a large-scale effort by some of the leading researchers in both communities to foster communication, education and collaboration between them, thereby advancing both fields and ultimately solving some of the deepest problems in physics. The overarching scientific questions motivating the Collaboration include:

  • Does spacetime emerge from entanglement?
  • Do black holes have interiors?
  • Does the universe exist outside our horizon?
  • What is the information-theoretic structure of quantum field theories?
  • Can quantum computers simulate all physical phenomena?
  • How does quantum information flow in time?

Bong Lian (Mathematics) is a member of the Simons Collaboration on Homological Mirror Symmetry, which involves nine investigators from eight different institutions in three countries. Mirror Symmetry, first discovered by theoretical physicists in late ‘80s, is a relationship between two very different-looking physical models of Nature, a remarkable equivalence or “duality” between different versions of a particular species of multidimensional space or shape (Calabi-Yau manifolds) that seemed to give rise to the same physics. People have been trying to give a precise and general mathematical description of this mirroring ever since, and in the process have generated a long list of very surprising and far-reaching mathematical predictions and conjectures. The so-called “Homological Mirror Symmetry Conjecture” (HMS) may be thought of as a culmination of these efforts, and Lian was a member of the group (including S.-T. Yau) that gave a proof of a precursor to HMS in a series of papers in the late ‘90s.

Lian and his Simons collaborators are determined to prove HMS in full generality and explore its applications. One consequence of HMS says that if one starts from a “complex manifold” (a type of even-dimensioned space that geometers have been studying since Riemann described the first examples in 1845), then all its internal geometric structures can in fact be described using a certain partner space, called a “symplectic manifold”. The latter type of space was a mathematical edifice invented to understand classical physics in the mid-1900s. This connection goes both ways: any internal geometric structure of the symplectic partner also has an equally compelling description using the original complex partner. No one had even remotely expected such a connection, especially given that the discoveries of the two types of spaces — complex and symplectic — were separated by more than 100 years and were invented for very different reasons. If proven true, HMS will give us ways to answer questions about the internal geometric structure of a complex manifold by studying its symplectic partner, and vice versa.

Proving HMS will also help resolve many very difficult problems in enumerative geometry that for more than a century were thought to be intractable. Enumerative geometry is an ancient (and until recently moribund) branch of geometry in which people count the number of geometric objects of a particular type that can be contained inside a space. Mirror symmetry and HMS have turned enumerative geometry into a new way to characterize and relate shapes and spaces.

Yoshinori Ohsumi to Receive Rosenstiel Award Wednesday, April 6

4 04 2016

ohsumi220Biologist Yoshinori Ohsumi will receive the 45th Rosenstiel Award for Distinguished Work in Biomedical Science this Wednesday, April 6th at 4:00 pm in Gerstenzang 123. At that time, he will present a lecture titled, “Lessons from yeast: Cellular recycling system, autophagy”.

Ohsumi is a cell biologist and professor at the Tokyo Institute of Technology’s Frontier Research Center in Japan. He is one of leading experts in the world on autophagy, a process that allows for the degradation and recycling of cellular components. The Rosenstiel Award is being given to Ohsumi in recognition of his pioneering discoveries in autophagy.

Learn more about Professor Ohsumi and his research at BrandeisNow.

SPROUT Continues Growing Support for Brandeisian Innovators

19 02 2016

Lil_Sprout_smallProgram Will Bestow Up to $100,000 to Promising Research Proposals

Could your research impact the world or do you have an idea that could create positive change? Need funding? SPROUT can help with that.

The popular SPROUT program, now in its sixth year, has announced increased funding for the 2016 round of proposals. SPROUT is funded by the Office of the Provost and run by Office of Technology Licensing. This year the Hassenfeld Family Innovation Center, recently created to support entrepreneurial and innovative collaborations happening across campus, contributed an additional $50,000 to be disbursed among the most promising requests.

Historically, the program has supported a diverse scope of lab-based innovations from all departments in the sciences  including Biology, Biochemistry, Physics, and Chemistry.  Past candidates have proposed projects ranging  from early‐stage research and development to patent‐ready projects ranging from treatments for diseases to lab tools.  Brandeis lab scientists have pitched their projects, including HIV vaccines (Sebastian Temme, Krauss lab),  neuroslicers (Yasmin Escobedo Lozoya, Nelson lab) and the use of carrot fiber as an anti-diabetic  (Michelle Landstrom, Hayes lab) to a panel of distinguished, outside judges. A SPROUT award can jumpstart your innovation and lead to continued opportunities. SPROUT awardees researching the use of carrot fiber as an anti-diabetic food agent were just awarded additional funding by the Massachusetts Innovation Commercialization Seed Fund program.

Other successful projects include “Enzymatic Reaction Recruits Chiral Nanoparticles to Inhibit Cancer Cells” led by Xuewen Du from the Xu lab, “Semaphorin4D: a disease‐modifying therapy for epilepsy” led by Daniel Acker of the Paradis lab, “X‐ray transparent Microfluidics for Protein Crystallization” led by Achini  Opathalage from the Fraden lab and “New and Rational Catalyst Development for Green Chemistry”  from the Thomas lab.  Those interested in learning more about past SPROUT winners are invited to read this recent Brandeis NOW article. A list of additional winners, along with their executive summaries, is available on the Brandeis OTL website.

Teams seeking support for scientific projects which require bench research, lab space, and/or lab equipment are encouraged to submit an abstract prior to the March 7 deadline. The competition is open to the entire Brandeis community including faculty, staff, and students. The Office of Technology Licensing will conduct information sessions on Thursday, February 25th 11:30 a.m.‐12:30 p.m. in Volen 201 and on Monday, February 29th 1:00 p.m.‐2:00 p.m. at the Shapiro Science Center, 1st Floor Library. Staff will address the application process as well as specific questions and interested applicants are highly encouraged to attend.

More details regarding the SPROUT awards, process and online application may be found at

Lipids hit a “sweet spot” to direct cellular membrane remodeling.

14 02 2016

Lipid membrane reshaping is critical to many common cellular processes, including cargo trafficking, cell motility, and organelle biogenesis. The Rodal lab studies how dynamic membrane remodeling is achieved by the active interplay between lipids and proteins. Recent results, published in Cell Reports, demonstrate that for the membrane remodeling protein Nervous Wreck (Nwk), intramolecular autoregulation and membrane charge work together in surprising ways to restrict remodeling to a limited range of lipid compositions.

F-BAR (Fes/Cip4 homology Bin/Amphiphysin/Rvs) domain family proteins are important mediators of membrane remodeling events. The F-BAR domain forms a crescent-shaped α-helical dimer that interacts with and deforms negatively charged membrane phospholipids by assembling into higher-order scaffolds. In this paper, Kelley et al. have shown that the neuronal F-BAR protein Nwk is autoregulated by its C-terminal SH3 domains, which interact directly with the F-BAR domain to inhibit membrane binding. Until now, the dogma in the field has been that increasing concentrations of negatively charged lipids would increase Nwk membrane binding, and thus would induce membrane deformation.

Surprisingly, Kelley et al. found that autoregulation does not mediate this kind of simple “on-off” switch for membrane remodeling. Instead, increasing the concentration of negatively charged lipids increases membrane binding, but inhibits F-BAR membrane deforming activities (see below). Using a combination of in vitro assays and single particle electron microscopy, they found that the Nwk F-BAR domain efficiently assembles into higher-order structures and deforms membranes only within “sweet spot” of negative membrane charge, and that autoregulation elevates this range. The implication of this work is that autoregulation could either reduce membrane binding or promote higher-order assembly, depending on local cellular membrane composition. This study suggests a significant role for the regulation of membrane composition in remodeling.

Authors on the study included Molecular and Cell Biology graduate students Charlotte Kelley and Shiyu Wang, staff member Tania Eskin, and undergraduate Emily Messelaar ’13 from the Rodal lab; postdoctoral fellow Kangkang Song, Associate Professor of Biology Daniela Nicastro (currently at UT Southwestern), and Associate Professor of Physics Michael Hagan.

DIY your own Programmable Illumination Microscope

22 01 2016

The Fraden Group describes how to build your own Programmable Illumination Microscope in the American Journal of Physics

Have you ever marveled at the equipment used in a research lab? Have you ever wondered how a specialized piece of equipment was made? Have you ever wondered how much it would cost to build your own research microscope? Have you ever considered trying to make your own research microscope? The details on how the Fraden Group builds their Programmable Illumination Microscope for under $4000 was recently published in the American Journal of Physics.

The Programmable Illumination Microscope or PIM is a highly specialized microscope where the illumination for the sample being imaged comes from a modified commercial projector, nearly identical to the ones mounted in every classroom. For the PIM the lens that projects the image onto the screen is removed and replaced with optics (often the same lens in reverse) that shrinks the image down so that it can be focused through the microscope objective onto the sample. The light coming from the projector, which is the illumination source for the microscope, can be modified in realtime based on the image being captured by the camera. Thus the illumination is not only programmable but can also be algorithmic and provide active feedback.

This new publication in the American Journal of Physics, which is published by the American Association of Physics Teachers, is intended to help small teaching and research labs across the country develop their own PIMs to be built and used by undergraduate students. The paper includes schematics and parts lists for the hardware as well as instructions and demonstration code for the software. Any other questions can be directed to the authors Nate Tompkins and Seth Fraden.

Nature News Feature Highlights Dogic Lab Active Matter Research

6 01 2016
Click to view slideshow.


Biological material is constantly consuming energy to make things move, organize information such as DNA, or divide cells for reproduction; but building a fundamental theory which encompasses all of the features of biological matter is no easy task. The burgeoning field of active matter aims to understand these complex biological phenomena through physics. Active matter research has seen rapid growth over the last decade, but linking existing active matter theories with experimental tests has not been possible until recently. An explosion of biologically based and synthetic experimental systems as well as more detailed theories have arrived in recent years, and some of these foundational experiments have been conducted here at Brandeis University. Recently, a Nature News Feature (The Physics of Life) has highlighted work from Zvonimir Dogic’s lab in an article about the field of active matter and the physics which endeavors to understand biology.


Resolving the magnetic field around the galaxy’s central black hole

7 12 2015
Credit: M. Weiss/CfA

Credit: M. Weiss/CfA

On December 4, the journal Science (Vol. 350 no. 6265 p 1242) published a paper titled, “Resolved magnetic-field structure and variability near the event horizon of Sagittarius A*” (abstract). The paper reports that the Event Horizon Telescope has detected strong magnetic fields around the supermassive black hole at the center of the Milky Way galaxy. John Wardle, Professor of Astrophysics at Brandeis, is one of the lead authors. A co-author is Michael Kosowsky ’14, who worked on the project as a summer research project at the MIT-Haystack observatory as a junior physics major, and is now an NSF Graduate Research Fellow at Harvard.

Near a black hole, differential rotation of a magnetized accretion disk is thought to produce an instability that amplifies weak magnetic fields, driving accretion and outflow. These magnetic fields would naturally give rise to the observed synchrotron emission in galaxy cores and to the formation of relativistic jets, but no observations to date have been able to resolve the expected horizon-scale magnetic-field structure. The paper reports interferometric observations (made with antennas in Hawaii, California and Arizona) at 1.3-millimeter wavelength that spatially resolve the linearly polarized emission from the Galactic Center supermassive black hole, Sagittarius A*. We have found evidence for partially ordered magnetic fields near the event horizon, on scales of ~6 Schwarzschild radii, and we have detected and localized the intra-hour variability associated with these fields.

The above image is an artist’s impression. With the planned addition of antennas in Mexico, Chile, Europe and the South Pole, the Event Horizon Telescope will be able to make true images with angular resolution of a few tens of microarcseconds.

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