Susan Lovett elected to the American Academy of Arts and Sciences

Susan LovettSusan Lovett, the Abraham S. and Gertrude Burg Professor of Microbiology, has been elected to the American Academy of Arts and Sciences. She was among the 276 outstanding individuals that were elected to the Academy in 2020 and announced on April 23. Brandeis University Professor, Anita Hill, joins Professor Lovett as a 2020 member of AAAS.

The Lovett lab studies the fundamental mechanisms by which cells preserve genetic information by the study of DNA damage repair and mutation avoidance in the model organism Escherichia coli. Additionally, they research how cell cycle events including DNA replication and chromosome segregation are coupled to cellular physiology and to the status of the chromosome.

Lovett joins other Brandeis science faculty members: Jeff Gelles, Gina Turrigiano, James Haber, Michael Rosbash, Eve Marder, David Derosier, Gregory Petsko, Stanley Deser, and Edgar Brown, Jr.

Founded in 1780, the Academy recognizes the outstanding achievements of individuals in academia, the arts, business, government, and public affairs.

Read more: BrandeisNow

DNA molecules tell nanoparticles how to self-assemble

Nature uses self-assembly to make a diversity of complex structures, such as biomolecules, virus shells, and cytoskeletal filaments. Today a key challenge is to translate this assembly process to artificial systems. DNA-coated nanoparticles provide a particularly promising approach to realizing this vision, since the base sequences can be designed to encode the formation of a chosen structure.

A recent publication from the Rogers Lab shows that interactions between DNA-coated particles can be encoded using DNA oligomers dispersed in solution that bind the particles together.  By changing the linker sequences in solution, Ph.D. students Janna Lowensohn and Alex Hensley showed that the same set of components can be directed to form a variety of different crystal structures. Going forward, this approach may be used to create programmable materials that can sense and respond to their environment.

 

DNA instructions

Paper: Self-Assembly and Crystallization of DNA-Coated Colloids via Linker-Encoded Interactions. Lowensohn J, Hensley A, Perlow-Zelman M, Rogers WB. Langmuir. 2020 Feb 18. doi: 10.1021/acs.langmuir.9b03391. (PubMed abstract)

Shinji Rho named 2020 Goldwater Scholar

Shinji Rho, Brandeis UndergraduateCongratulations to Shinji Rho who has been named a 2020 Goldwater Scholar.  The Goldwater Scholarship is a national scholarship designed to encourage outstanding students in their sophomore and junior year to pursue research careers in the fields of mathematics, the natural sciences, and engineering.

Shinji is currently a junior. Her project at Brandeis is on a transcriptional activator Gal4, which binds to upstream activating sequence (UAS) sites in the yeast genome to promote transcription. Previous studies have shown that dwell time of Gal4 on the UAS is significantly longer in purified systems than in cells. She is interested in finding the reason for this dwell time difference using single-molecule light microscopy. The findings of her project will provide a more realistic view of how transcription activation system behaves when nuclear proteins are present. 

Shinji plans to obtain a PhD degree in cancer biology, ultimately conducting research on developing more accurate and easily accessible breast cancer diagnosis methods.

Her mentor is Jeff Gelles, Aron and Imre Tauber Professor of Biochemistry and Molecular Pharmacology.

 

Autism-linked Gene Keeps Brains in Balance

Mutations in the human Shank3 gene – so called “Shankopathies” – are strongly associated with Autism-spectrum disorders and intellectual disability, and appear to increase risk for a number of other disorders such as bipolar disorder and epilepsy. How it is that loss of function of this single gene generates pervasive disfunction within the neural circuits that underlie cognition and behavior is not understood. Now a recent report from the Turrigiano lab at Brandeis (Autism-Associated Shank3 Is Essential for Homeostatic Compensation in Rodent V1. Neuron. 2020 Mar 10. ) sheds light into this process, by showing how Shank3 loss disables mechanisms that normally act to keep brain circuitry in balance. Much as your body maintains a constant temperature through the use of internal thermostats and negative feedback mechanisms, brain circuits maintain balanced activity – neither too low and unresponsive, nor too high and hyperactive – by using a set of so-called “homeostatic” plasticity mechanisms to keep circuit excitability within an ideal range. This process is especially important during childhood and adolescence, because developing circuits can easily get out of balance as brain circuitry changes as a result of normal developmental processes.

Using mouse and rat models of human Shankopathies, the team, led by Research Associate Vedakumar Tatavarty, found that loss of Shank3 disables these homeostatic plasticity mechanisms and prevents brain circuits from compensating for changes to sensory drive. These defects in homeostatic plasticity are due to acute loss of Shank3 within individual neurons, meaning they are not an indirect effect of messed-up circuit wiring caused by loss of the gene throughout development. This finding suggests that Shank3 is a fundamental part of the cellular machinery that normally mediates homeostatic plasticity. The team went on to show that homeostatic plasticity could be restored after Shank3 loss by treatment with Lithium – a drug with a long history of use to treat neuropsychiatric disorders such as bipolar disorder – and that Lithium was also able to reduce a repetitive grooming behavior in mice that lack Shank3. These mice normally groom to excess, even to the point of self-injury, but a week of lithium treatment was able to reduce grooming to normal levels.

So do these findings suggest that Lithium might be useful in treating human Shankopathies? While Lithium remains the frontline treatment for some human disorders such as bipolar disorder, it is not well-tolerated, says Turrigiano, “and of course we cannot extrapolate from findings in mice directly to humans. Instead, we hope to use Lithium as a tool to reveal the pathways that can restore homeostatic plasticity in Shankopathies, which in the long term may allow us to design better, more specific interventions”. Defects in homeostatic plasticity have been implicated in a wide range of human brain disorders ranging from Autism spectrum disorders to Alzheimer’s disease, so these studies are likely to have important implications for overall brain health.

Autism-Associated Shank3 Is Essential for Homeostatic Compensation in Rodent V1. Tatavarty V, Torrado Pacheco A, Groves Kuhnle C, Lin H, Koundinya P, Miska NJ, Hengen KB, Wagner FF, Van Hooser SD, Turrigiano GG. Neuron. 2020 Mar 10. pii: S0896-6273(20)30184-7. doi: 10.1016/j.neuron.2020.02.033.

The Rogers Lab receives a prestigious international grant to study the origin of life

HFSP logoProfessor W. Benjamin Rogers in the Department of Physics has been awarded a 2020 Human Frontier Science Program (HFSP) collaborative Program Grant to create a self-propagating synthetic cell. The HFSP Program Grants aim to tackle big questions in the life sciences by supporting and bringing together researchers with different backgrounds from different countries. Professor Rogers’ team grant was one of 20 successful Program Grants that went through a year-long global selection process.

The project aims to build a stably-propagating cell from simple components. The cell will have a lipid membrane encapsulating DNA and transcription-translation machinery, and be able to grow and divide by internally synthesizing its own membrane material.

The project is significant because a stably propagating cell is a vital element of natural selection. Extant life on Earth is a consequence of natural selection acting upon earlier forms of life, shaping the lineages over time. Thus at some point early in life’s origins, a sustainably propagating cell must have emerged, allowing selective advantages to accumulate over successive generations. For daughter cells to have retained the attributes of their parent, both the genetic information and the cell contents must have been replicated with reasonable fidelity.  However, it is currently unclear how controlled cell division could have first emerged from relatively simple molecules. It is precisely this mystery that the team hopes to understand by attempting to recreate it in a test tube.

Professor Rogers’ grant is shared with Dr. Yutetsu Kuruma from Japan Agency for Marine-Earth Science and Technology and Professor Anna Wang from University of New South Wales in Australia.

Gelation without Attraction

By Bulbul Chakraborty

Gels are one of the most puzzling of all solids. Originally coined as a short form of gelatin, gels can be jelly-like as in Jello, or quite hard as in silica gels. They appear in suspensions of particles at extremely low volume fractions, and yet they are rigid. The conventional wisdom is that gels are a consequence of arrested phase separation of the suspended particles from the fluid. A natural mechanism for the arrest is attraction between the particles, which leads to the formation of filamentous networks of particles weaving through the suspending fluid.

Attraction has been viewed as being essential to the formation of gels. However, a new study published in Physical Review Research led by Carl Merrigan from the Chakraborty group, shows that “active particles” can gel even in the absence of physical attraction. Active matter, composed of particles that convert ambient energy to directed motion, has emerged as an important model for the collective behavior of biological matter such as bacterial suspensions. Using a combination of theoretical analysis and numerical simulations, the collaboration between the groups of Chakraborty and Shokef (Tel Aviv University) showed that the directed motion acts like an effective attraction, leading to gelation of the active particles.

The figure below shows the structure of these gels. As the particles become more active, they jam into clusters of immobile particles (red) surrounded by fluid regions (blue), and often opening up voids. Intriguingly, these active particles, which repel each other also show a transition from a dense glassy solid to a gel as the speed of directed motion is increased. The remarkable similarity between the behavior of passive particles with attraction and active particles suggests that biological entities could form solid-like aggregates without any physical or chemical attraction, purely as a consequence of their dynamics.

Reasearch image from Gelation without Attraction post

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