Using computer simulations to model bacterial microcompartment assembly

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

Jeffery Kelly to receive the 2016 Jacob and Louise Gabbay Award

jefferywkelly

Jeffery W. Kelly

Jeffery W. Kelly, the Lita Annenberg Hazen Professor of Chemistry, and Chairman of the Department of Molecular and Experimental Medicine at the Scripps Research Institute, has been selected to receive the 2016 Jacob and Louise Gabbay Award in Biotechnology and Medicine “in recognition of his profound and paradigm-shifting contributions to our understanding of protein folding mechanisms and protein misfolding diseases”.

The award, administered by the Rosenstiel Center at Brandeis, consists of a $15,000 cash prize and a medallion. Dr. Kelly will deliver the award lecture on “The Chemistry and Biology of Adapting Proteostasis for Disease Intervention” in the Shapiro Campus Center Theater at 4:00PM, on Thursday, September 29, 2016.

The Kelly Group focuses their research on understanding the principles of protein folding and comprehending the basis for misfolding diseases. They strive to develop novel therapeutic strategies using chemistry, biophysical and cell biology approaches.

 

Marder, Shatz, and Merzenich share 2016 Kavli Prize in Neuroscience

Eve MarderBreaking news: The 2016 Kavli Prize in Neuroscience is awarded to Eve Marder (Brandeis), Carla Shatz (Stanford), and Michael M. Merzenich (UCSF), “for the discovery of mechanisms that allow experience and neural activity to remodel brain function.”

 

Trapping individual cell types in the mouse brain

Lines labeling cortical subplate, mesencephalic, and diencephalic cell types

Lines labeling cortical subplate, mesencephalic, and diencephalic cell types (see Fig. 7 in Shima et al.)

The complexity of the human brain depends upon the many thousands of individual types of nerve cells it contains. Even the much simpler mouse brain probably contains 10,000 or more different neuronal cell types. Brandeis scientists Yasu Shima, Sacha Nelson and colleagues report in the journal eLife on a new approach for genetically identifying and manipulating these cell types.

Cells in the brain have different functions and therefore express different genes. Important instructions for which genes to express, in which cell types, lie not only in the genes themselves, but in small pieces of DNA called enhancers found in the large spaces between genes. The Brandeis group has found a way to highjack these instructions to express other artificial genes in particular cell types in the mouse brain. Some of these artificially expressed genes (also called transgenes) simply make the cells fluorescent so they can be seen under the microscope. Other transgenes are master regulators that can be used to turn on or off any other gene of interest. This will allow scientists to activate or deactivate the cells to see how they alter behavior, or to study the function of specific genes by altering them only in some cell types without altering them everywhere in the body. In addition to developing the approach, the Brandeis group created a resource of over 150 strains of mice in which different brain cell types can be studied.

website: enhancertrap.bio.brandeis.edu

Shima Y, Sugino K, Hempel C, Shima M, Taneja P, Bullis JB, Mehta S, Lois C, Nelson SB. A mammalian enhancer trap resource for discovering and manipulating neuronal cell types. eLife. 2016;5.

Simons Foundation funds Brandeis Math, Physics collaborations

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.

Two Science Students Are Fulbright Fellows

Two of the five Brandeis undergraduates and recent alumni that have been selected to teach English overseas as Fulbright Fellows are Division of Science students.

Abby Brooks ’16 and Joel Burt-Miller ’16 have received English Teaching Assistantships through the Fulbright grant program. Brooks is a double major in biology and history. She will be teaching in Laos. Joel Burt-Miller ’16 is a double major in biology and Health: Science, Society and Policy. He will be teaching in India.

Find more information about our soon-to-be graduates and the Fulbright program on BrandeisNow.

7th Annual Jay Pepose Award to be presented April 12 at 12:30 pm

David WilliamsDavid Williams from the University of Rochester has been selected to receive the 7th annual Jay Pepose ’75 Award in Vision Sciences. Williams will be presented with the Pepose award on Tuesday, April 12th at 12:30 pm in Gerstenzang 121. The celebration will include David Williams talk titled, “Seeing Through the Retina”.

Williams’ research has improved the effectiveness of laser refractive surgery, the design of contact lenses, and enabled the imaging of single cells in the retina.

Yoshinori Ohsumi to Receive Rosenstiel Award Wednesday, April 6

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.

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