JBS Offers “Bio-Inspired Design” Course

Maria de Boef Miara, Lecturer in Biology at Brandeis University, will be leading a course titled Bio-Inspired Design this summer (June 1 thru August 7, 2015). Bio-Inspired Design is part of the Justice Brandeis Semester (JBS). JBS combines courses and experiential learning to provide complete, immersive experiences so students can deeply examine a specific area of study.

Bio-Inspired Design is designed for students from a wide spectrum of disciplines, but may be particularly appealing to students in Biology, Biological Physics, Environmental Studies or HSSP areas. This is a 10-week course providing 12 credits.

Students in Bio-Inspired Design will spend the summer working with biologists, engineers and artists in a variety of settings. They will explore intriguing life forms and develop the quantitative tools needed to work at the intersection of form and function.

Simulations Say Viral Genome Lengths are Optimal for Capsid Assembly

Viruses are infectious agents made up of proteins and a genome made of DNA or RNA. Upon infecting a host cell, viruses hijack the cell’s gene expression machinery and force it to produce copies of the viral genome and proteins, which then assemble into new viruses that can eventually infect other host cells. Because assembly is an essential step in the viral life cycle, understanding how this process occurs could significantly advance the fight against viral diseases.

In many viral families, a protein shell called a capsid forms around the viral genome during the assembly process. Capsids can also assemble around nucleic acids in solution, indicating that a host cell is not required for their formation. Since capsid proteins are positively charged, and nucleic acids are negatively charged, electrostatic interactions between the two are thought to be important in capsid assembly. Current questions of interest are how structural features of the viral genome affect assembly, and why the negative charge on viral genomes is actually far greater than the positive charge on capsids. These questions are difficult to address experimentally because most of the intermediates that form during virus assembly are too short-lived to be imaged.

hagan-capsid-sim

Snapshots from a computer simulation in which model capsid subunits (blue) assemble around a linear, negatively charged polymer (red). Positive charges on the capsid proteins are shown in yellow.

In a new paper in eLife, Brandeis postdoc Jason Perlmutter, Physics grad student Cong Qiao, and Associate Professor Michael Hagan have used state of the art computational methods and advances in graphical processing units (on our High Performance Computing cluster) to produce the most realistic model of capsid assembly to date. They showed that the stability of the complex formed between the nucleic acid and the capsid depends on the length of the viral genome. Yield was highest for genomes within a certain range of lengths, and capsids that assembled around longer or shorter genomes tended to be malformed.

Perlmutter et al. also explored how structural features of the virus — including base-pairing between viral nucleic acids, and the size and charge of the capsid — determine the optimal length of the viral genome. When they included structural data from real viruses in their simulations and predicted the optimal lengths for the viral genome, the results were very similar to those seen in existing viruses. This indicates that the structure of the viral genome has been optimized to promote packaging into capsids. Understanding this relationship between structure and packaging will make it easier to develop antiviral agents that thwart or misdirect virus assembly, and could aid the redesign of viruses for use in gene therapy and drug delivery.

Perlmutter JD, Qiao C, Hagan MF. Viral genome structures are optimal for capsid assembly. eLife 2013;2:e00632

Dogic Lab Wins Andor Insight Award

The ‘Insight Awards‘  is a video contest showcasing research imagery from the physical and life sciences which utilize Andor technology to capture data.  This year, the Dogic Lab submitted a research video to the competition and garnered first prize in the Physical Sciences division for their video of Oscillating Microtubule Bundles.

From the competition notes:

Microtubules are a bio-polymer composed of the protein tubulin and are used extensively in the cell for cellular division, cell motility, and transportation of cargo within the cell. Here, we investigate the material properties of mixtures of microtubules, a depletion agent, and the molecular motor Kinesin. The microtubules, driven by Kinesin motors, spontaneously organize into bundles of microtubules that oscillate in a manner reminiscent of flagella and cilia found in biology. This engineered system will allow us to studying systems of self-propelled and self-organized matter that exist far from equilibrium in the field known as Active Matter.

We use standard fluorescent microscopy to image labeled microtubules in a thin, flow cell microscope chamber. An Andor Clara camera was used in conjunction with a Nikon Ti Eclipse microscope to capture this video.

Video and Entry by Stephen DeCamp.

For this, and more videos from the Dogic Lab, visit their YouTube page or their website at Brandeis University.

Materials in Motion: Engineering Bio-Inspired Motile Matter

Life is on the move! Motion is ubiquitous in biology. From the gargantuan steps of an elephant to the tiniest single celled amoeba, movement in biology is a complex phenomenon that originates at the cellular level and involves the organization and regulation of thousands of proteins. These proteins do everything from mixing the cytoplasm to driving cell motility and cell division. Deciphering the origins of motion is no easy feat and scientists have been studying such complex behavior for quite some time. With biology as an inspiration, studying these complex behaviors provides insight into engineering principals which will allow researchers to develop an entirely new category of far-from-equilibrium materials that spontaneously move, flow or swim.

In a recent report in the journal Nature, a team of researchers from Brandeis University consisting of Tim Sanchez, Daniel T. N. Chen, Stephen J. DeCamp, Michael Heymann, and Zvonimir Dogic have constructed a minimal experimental system for studying far-from-equilibrium materials. This system demonstrates the assembly of a simple mixture of proteins that results in a hierarchy of phenomena. This hierarchy begins with extending bundles of bio-filaments, produces networks that mix themselves, and finally culminates in active liquid crystals that impart self-motility to large emulsion droplets.

Their system consists of three basic components: 1) microtubule filaments, 2) kinesin motor proteins which exert forces between microtubule filaments, and 3) a depletion agent which bundles microtubule filaments together. When put together under well-defined conditions, these components form bundled active networks (BANs) that exhibit large-scale spontaneous motion driven by internally generated active stresses. These motions, in turn, drive coherent fluid flows. These features bear a striking resemblance to a biological process called cytoplasmic streaming, in which the cellular cytoskeleton spontaneously mixes its content. Additionally, the system has great potential for testing active matter theories because the researchers can precisely tune the relevant system parameters, such as ATP and protein concentration.

 

The researchers also demonstrate the utility of this biologically-inspired synthetic system by studying materials science topics that have no direct biological analog. Under dense confinement to an oil-water interface, microtubule bundles undergo a spontaneous transition to an aligned state. Soft matter physics describes such materials as liquid crystals, which are the materials used to make liquid crystal displays (LCDs). These active liquid crystals show a rich variety of dynamical behavior that is totally inaccessible to their equilibrium analogs and opens an avenue for studying an entirely new class of materials with highly desirable properties.

Lastly, inspired by streaming flows that occur in cells, the researchers encapsulate the bundled active networks into spherical emulsion droplets. Within the droplet, microtubules again formed a self-organized nematic liquid crystal at the oil-water interface. When the droplets were partially squished between glass plates, the streaming flows generated by the dynamic liquid crystals lead to the emergence of spontaneous self-motility.

This research constitutes several important advances in the studies of the cytoskeleton, non-equilibrium statistical mechanics, soft-condensed matter, active matter, and the hydrodynamics of fluid mixing. The researchers have demonstrated the use of biological materials to produce biomimetic functions ranging from self-motility to spontaneous fluid flows using fundamentally new mechanisms. Additionally, the experimental system of bundled active microtubules is poised to be a model for exploring the physics of gels, liquid crystals, and emulsions under far-from-equilibrium conditions.

To see more videos from the Dogic lab at Brandeis University, check out their YouTube page.

Applications open for HHMI Interfaces Scholar Award Lecturer

The Quantitative Biology Program at Brandeis University, supported by a grant from Howard Hughes Medical Institute, is now accepting applications for an award for preparing an outstanding set of three pedagogical lectures on a subject at the interface of the physical and biomedical sciences.  These lectures will be given at the Quantitative Biology Bootcamp, January 26, through January 27, 2013.  The award consists of a cash prize of $2,000.

Any graduate student or postdoctoral research associate currently at Brandeis is eligible to apply.  The application packet should consist of short  curriculum vitae and a one page outline of the three lectures.  QB faculty will work with the successful applicant in preparing the lectures.  Applications should be submitted to Jen Scappini, (jscappin at brandeis dot edu). Due date will be discussed at meeting.

An information session for potential applicants will be held on Friday, October 26th, 9:30-10:00 in Kosow 207

A list of past winners and links to their lecture presentations can be found at http://www.brandeis.edu/programs/quantbio/interdisciplinary.html

 

Quantitative Biology Bootcamp 2012

What do dinosaur DNA, calculating the global amount of carbon dioxide consumed in photosynthesis, and cooperation and cheating between yeast cells have in common?  They were all topics discussed at the sixth annual Quantitative Biology Bootcamp, held on the Brandeis campus January 12 and 13.

At the bootcamp, more than 40 Ph.D. students and faculty participated in lectures, discussions, and computational projects using both computers and pencil-on-paper approaches.  The Brandeis Quantitative Biology Program is a unique “add-on” graduate program open to students in all six of the natural sciences Ph.D. programs at Brandeis.  The main goal of the program is to train students to work effectively as a part of research teams that span the boundaries of traditional scientific disciplines.  To this end, Quantitative Biology students participate in both courses and out-of-classroom activities, like the Bootcamp, that highlight the diverse approaches to scientific problems taken by scientists from different disciplines.

A central feature of this year’s Bootcamp were the lectures and computer laboratory exercise presented by Jeffrey Boucher, a student in the Biochemistry Ph.D. program and the winner of Quantitative Biology Program’s 2012 HHMI Interfaces Scholar Award.  Boucher’s presentations described mathematical techniques and experimental methods that can be used to understand the processes of biological evolution by reconstructing genes and proteins present in the long-extinct progenitors of present animal, plant and microbial species. Prospective graduate students and others interested in learning more about Brandeis Quantitative Biology can consult the program’s web site at http://www.brandeis.edu/programs/quantbio/index.html

Quantitative Biology Lecture Prize

The Quantitative Biology Program at Brandeis University, supported by a grant from Howard Huges Medical Institute, is now soliciting applications for an award for preparing an outstanding set of three pedagogical lectures on a subject at the interface of the physical and biomedical sciences.  These lectures will be given at the Quantitative Biology Boot camp, January 12, through Friday, January 13, 2012.  The award consists of a cash prize of $2,000.

Any graduate student or postdoctoral research associate currently at Brandeis is eligible to apply.  The application packet should consist of short/ curriculum vitae/ and a one page outline of the three lectures.  QB faculty will work with the successful applicant in preparing the lectures.  Applications should be submitted  to Jen Scappini either by campus mail (MS009), or e-mail (jscappin@brandeis.edu). (Due date will be discussed at the Wednesday, 10.19.11 Meeting).

An information session for potential applicants will be held on Wednesday, October 19th, 2:30-3:00 in Kosow 207.

Microtubules and Molecular Motors Do The Wave

Most people are familiar with audiences in crowded arenas performing “the wave,” raising their hands in sync to produce a pattern that propagates around the whole stadium.  This self-organized motion appears seemingly out of nowhere.  It is not produced by any external control, but is rather emerges from thousands of individuals interacting only with their neighbors.  A similar principle of self-organization might also be relevant on length scales that are billion times smaller.  On this scale, nanometer-sized proteins interact with each other to produce dynamical structures and patterns that are essential for life—and some of these processes are reminiscent of waves in crowded stadiums.  For example, thousands of nano-sized molecular motors located within a single eukaryotic flagellum or cilium coordinate their activity to produce wave-like beating patterns.  Furthermore, dense arrays of cilia spontaneously synchronize their beating to produce metachronal waves.

Proper functioning of cilia is essential for health; for example, cilia determine the correct polarity and location of our organs during development.  Defective cilia can cause a serious condition called situs inversus, in which the positions of the heart and lungs are mirrored from the normal state.  In another example, thousands of cilia in our lungs function to clear airways of microscopic debris such as dust or smoke by organizing their beating into coordinated, wave-like patterns.  Despite the importance of ciliar function, the exact mechanisms that lead to spontaneous wave-like patterns within isolated cilia, as well as in dense ciliary fields, is not well understood.

In a paper published in the journal Science this week, an interdisciplinary team consisting of physics graduate student Timothy Sanchez and biochemistry graduate student David Welch working with biophysicist Zvonimir Dogic and biologist Daniela Nicastro present a striking finding: the first example of a simple microscopic system that self-organizes to produce cilia-like beating patterns.  Their experimental system consists of three main components: 1) microtubule filaments; 2) motor proteins called kinesin, which consume chemical fuel to move along microtubules; and (3) a bundling agent that induces assembly of filaments into bundles.  Sanchez et al. found that under a certain set of conditions, these very simple components are able to self-organize into active bundles that spontaneously beat in a periodic manner.  One large spontaneously beating bundle is featured below:

In addition to observing the beating of isolated bundles, the researchers were also able to assemble a dense field of bundles that spontaneously synchronized their beating patterns into traveling waves.  An example of this higher-level organization is shown here:

The significance of these observations is several-fold. First, due to the importance of ciliar function for health, there is great interest in elucidating the mechanism that controls the beating patterns of isolated cilia as well as dense ciliary fields.  However, the complexity of these structures presents a major challenge.  Each eukaryotic flagellum and cilium contains more than 600 different proteins.  For this reason, most previous studies of cilia and flagella have employed a top-down approach; they have attempted to elucidate the beating mechanism by deconstructing the fully functioning organelles through the systematic elimination ­­­of constituent proteins. In this study, the researchers utilize an alternative bottom-up approach and demonstrate for the first time that it is possible to construct artificial cilia-like structures from a “minimal system,” comprised of only three components.  These observations suggest that emergent properties, spontaneously arising when microscopic molecular motors interact with each other, might play a role in formation of ciliary beating patterns.

Second, self-organizing processes in general have recently become the focus of considerable interest in the physics community.  These processes range in scale from microscopic cellular functions and swarms of bacteria to macroscopic phenomena such as flocking of birds and manmade traffic jams. Theoretical models indicate that these vastly different phenomena can be described using similar theoretical formalisms.  However, controllable experiments with flocks of birds or crowds at football stadiums are virtually impossible to conduct.  The experiments described by Sanchez et al. could serve as a model system to test a broad range of theoretical predictions. Third, the reproduction of such an essential biological functionality in a simple in vitro system will be of great interest to the fields of cellular and evolutionary biology. Finally, these findings open the door for the development of one of the major goals of nanotechnology: to design motile nano-scale objects.

These encouraging results are only the first from this very new model system.  The Dogic lab is currently planning refinements to the system to study these topics in greater depth.

UPDATE: Today, this publication was additionally featured on NPR Science Friday as the video pick of the week:

 

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