Dynamics of GreB-RNA polymerase interaction

Larry Tetone, Larry Friedman, and Melissa Osborne, and collaborators from the Gelles lab (Brandeis University) and the Landick lab (University of Wisconsin-Madison) used multi-wavelength single-molecule fluorescence methods to for the first time directly observe the dynamic binding and dissociation of an accessory protein with an RNAP during active transcript elongation.

Their findings are detailed in the recent paper “Dynamics of GreB-RNA polymerase interaction.” (PNAS, published online 1/30/2017).

Read more at The Little Engine Shop blog

Mediating the early response to acute hypoxia

Neurons in the brain require a continuous supply of oxygen for normal activity. If the level of oxygen in the brain decreases—for example when a blood vessel becomes blocked—neurons begin to die, and permanent brain damage can result. A shortage of oxygen first causes sodium ion channels within the surface membrane of the neurons to open. Sodium ions then flow into the cells through these open channels to trigger a cascade of events inside the cells that ultimately results in their death.

In “SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons” (Elife), Plant et al. now reveal how oxygen deficiency, otherwise known as hypoxia, rapidly increases the flow of sodium ions into brain cells. By inducing hypoxia in neurons from rat brain, Plant et al. show that a lack of oxygen causes SUMOylation, a process whereby a series of enzymes work together to attach a Small Ubiquitin-like Modifier (or SUMO) protein, of specific sodium ion channels in under a minute. The channels linked to the SUMO protein, a subtype called Nav1.2, open more readily than unmodified channels, allowing more sodium ions to enter the neurons.

Plant et al. study granule cells of the cerebellum, the most numerous type of neuron in the human brain. Further investigation is required to determine if SUMOylation of Nav1.2 channels underlies the response of other neurons to hypoxia as well. It also remains to be discovered whether molecules that block the SUMOylation of Nav1.2 channels, or that prevent the flow of sodium ions through these channels, could reduce the number of brain cells that die in low-oxygen conditions such as stroke.

doi: 10.7554/eLife.20054.
SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons
Leigh D Plant, Jeremy D Marks, Steve AN Goldstein
eLife 2016;5:e20054

Research Funding For Undergrads: MRSEC Summer Materials Undergraduate Research Fellowships

The Division of Science wishes to announce that, in 2017, we will offer seven MRSEC Summer  Materials Undergraduate Research Fellowships (SMURF) for Brandeis students doing undergraduate research, sponsored by the Brandeis Materials Research Science and Engineering Center.

The fellowship winners will receive $5,000 stipends (housing support is not included) to engage in an intensive and rewarding research and development program that consists of full-time research in a MRSEC lab, weekly activities (~1-2 hours/week) organized by the MRSEC Director of Education, and participation in SciFest VII on Aug 3, 2017.

The due date for applications is February 27, 2017, at 6:00 PM EST.

To apply, the application form is online and part of the Unified Application: https://goo.gl/9LcSpG (Brandeis login required).


Eligibility

Students are eligible if they will be rising Brandeis sophomores, juniors, or seniors in Summer 2017 (classes of ’18, ’19, and ’20). No prior lab experience is required. A commitment from a Brandeis MRSEC member to serve as your mentor in Summer 2017 is required though. The MRSEC faculty list is: http://www.brandeis.edu/mrsec/people/index.html

Conflicting Commitments
SMURF recipients are expected to be available to do full time laboratory research between May 30 – August 4, 2017. During that period, SMURF students are not allowed to take summer courses, work another job or participate in extensive volunteer/shadowing experiences in which they commit to being out of the lab for a significant amount of time during the summer. Additionally, students should not be paid for doing lab research during this period from other funding sources.

Application Resources
Interested students should apply online (Brandeis login required). Questions that are not answered in the online FAQ may be addressed to Steven Karel <divsci at brandeis.edu>.

MRSEC offers 2 one-week courses in Summer 2017

Brandeis’ MRSEC is offering two one-week courses in June 2017. “Introduction to Microfluidics Technology” and “Biomaterials: Kinesin Production for Beginners” are both hands-on laboratory courses with no prerequisites.

  • Introduction to Microfluidics Technology
    Date: June 19-23, 2017
    This course is intended for graduate students, post docs, faculty, and industrial scientists/engineers interested in utilizing microfluidic technology in their work, both in the physical and life sciences
  • Biomaterials: Kinesin Production for Beginners
    Date: June 26-30, 2017
    This course is intended for graduate students, postdocs, faculty, and industrial scientists/engineers interested in laboratory-scale expression and purification of kinesins, the biomolecular motors that power Brandeis MRSEC’s highly regarded active liquid crystals. The course is suitable for non-biologists who do not have access to any major specialized equipment at their home institution, since the goal of the course is to make protein production accessible to a wider variety of labs.

Register early (by March 1) for a $50 discount. Regular registration for both courses closes March 31, 2017.

Both courses are sponsored by the National Science Foundation’s Bioinspired Soft Materials Research Science and Engineering Center (MRSEC) at Brandeis.

The Benefits of Middle Age

Almost all our cells harbor a sensory organelle called the primary cilium, homologous to the better known flagella found in protists. Some of these cilia can beat and allow the cell to move (eg. in sperm), or move fluid (eg. cerebrospinal fluid) around them. However, other specialized cilia such as those found in photoreceptor cells and in our olfactory neurons function solely as sensory organelles, providing the primary site for signal reception and transduction. The vast majority of our somatic cells display a short and simple rod-like cilium that plays crucial roles during development and in adulthood. For instance, during development, they are essential for transducing critical secreted developmental signals such as Sonic hedgehog that is required for the elaboration of cell types in almost every tissue (eg. in brain, bones, muscles, skin). In adults, cilia are required for normal functioning of our kidneys, and primary cilia in hypothalamic neurons have been shown to regulate hunger and satiety.

Given their importance, it is not surprising that defects in cilia structure and function lead to a whole host of diseases ranging from severe developmental disorders and embryonic lethality to hydrocephalus (fluid accumulation in the brain), infertility, obesity, blindness, and polycystic kidney among others. Often these diseases manifest early in development resulting in prenatal death or severe disability, but milder ciliary dysfunction leads to disease phenotypes later in life.

Much is now known about how cilia are formed and how they function during development. However, surprisingly, how aging affects cilia, and possibly the severity of cilia-related diseases, is not well studied. A new study by postdocs Astrid Cornils and Ashish Maurya, and graduate student Lauren Tereshko from Piali Sengupta’s laboratory, and collaborators at University College Dublin and University of Iowa, begins to address this question using the microscopic roundworm C. elegans (pictured below). These worms display cilia on a set of sensory neurons; these cilia are built by mechanisms that are similar to those in other animals including in humans. Worms have a life span of about 2-3 weeks, thereby making the study of how aging affects cilia function quite feasible.

benefits-midage

They find that cilia structure is somewhat altered in extreme old age in control animals. However, unexpectedly, when they looked at animals carrying mutations that lead to human ciliary diseases, the severely defective cilia seen in larvae and young adults displayed a partial but significant recovery during middle-age, a period associated with declining reproductive function. They went on to show that the heat-shock response and the ubiquitin-proteasome system, two major pathways required for alleviating protein misfolding stress in aging and neurodegenerative diseases, are essential for this age-dependent cilia recovery in mutant animals. This restoration of cilia function is transient; cilia structure becomes defective again in extreme old age. These results suggest that increased function of protein quality control mechanisms during middle age can transiently suppress the effects of some mutations in cilia genes, and raise the possibility that these findings may help guide the design of therapeutic strategies to target specific ciliary diseases. Some things can improve with aging!

How different metals stick together

Editor: Tamara Hanna JEM: Esther RTP: Bryan Nolte

Cover artwork from Inorganic Chemistry featuring paper from the Thomas group

Metal-metal interactions are at the heart of some of the most interesting metal-catalyzed transformations and are found everywhere from Nature (metalloenzymes) to industrially important heterogeneous catalysis (surfaces, nanomaterials).  While textbooks have been written about metal-metal multiple bonds, surprising gaps in knowledge remain, including bonding between first row transition metals and bonding between different metals.  The Thomas group in the Brandeis Chemistry Department seeks to fill these gaps in knowledge through the systematic synthesis of heterobimetallic complexes featuring a wide range of different transition metals and developing a thorough understanding of the electronic structure and bonding of these novel compounds.

The latest issue of Inorganic Chemistry features cover artwork highlighting the recent paper from the Thomas laboratory titled “Exploring Trends in Metal–Metal Bonding, Spectroscopic Properties, and Conformational Flexibility in a Series of Heterobimetallic Ti/M and V/M Complexes (M = Fe, Co, Ni, and Cu).” The paper describes an extensive study of a series of Ti/M and V/M heterobimetallic complexes, where M is systematically varied across the periodic table from left to right (Fe, Co, Ni, Cu).  These complexes are classified as “early/late” heterobimetallic complexes because they feature one metal from the left half of the periodic table (“early”) and one metal from the right half of the periodic table (“late”).  The inherent differences between the properties of the two metals makes their metal-metal bonding quite polar and sensitive to a variety of different factors, but also poises these compounds for interesting reactivity because of the two electronically different metal sites presented. This latest installation from the Thomas group uncovers trends in metal-metal bond distance determined using X-ray crystallography, and uses a variety of spectroscopic (EPR, NMR, Mossbauer) and computational tools to probe the electronic structure of these compounds.  Most interestingly, these compounds are shown to be conformationally flexible, with ligand rearrangements occurring rapidly in solution and this ligand hemilability, which is ideal for facilitating reactivity, can be correlated directly with the strength of metal-metal interactions.

This paper was highly collaborative and its preparation involved researchers from both Brandeis and Harvard University. The synthesis and characterization of the new compounds were largely carried out by Bing Wu, a graduate student in the Thomas group, along with Chris Thomas herself. Matt Wilding, a recent Ph.D. graduate student from the Betley laboratory at Harvard University, assisted with the collection and interpretation of Mossbauer data and designed the cover artwork. Recent Ph.D. graduate Mark Bezpalko, of the Thomas/Foxman groups, and Bruce Foxman carried out all of the structural work in the Brandeis X-ray Diffraction Facility, and all of the computational studies were carried out by Bing Wu and Chris Thomas using the Brandeis high performance cluster.

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