PLEASE NOTE: the paper by Anthony et al. in Structure was subsequently retracted due to the discovery of research misconduct by its first author, see http://www.cell.com/structure/abstract/S0969-2126(14)00016-1.
In economically turbulent times gold is acquired and held onto as a stable, secure commodity – it’s the “gold standard”. Gold of course has been a source of wealth as a precious metal and source of beauty. Importantly, gold is an incredibly dense and malleable transition metal that maintains its beauty and strength over long time periods, existing as a stable pure solid. Gold has also been an important subject of study and use in life science applications as well as in the physical sciences and in the clinical realm – not only as a source for fillings or a bridge after the dentist deals with your teeth issues!
Kelsey Anthony, a doctoral student in the Brandeis Biochemistry program as well at the Quantitative Biology program, has been working with gold in the Pomeranz Krummel lab to study biopolymer structure. The properties of gold most important in these applications are that it is a pure and stable solid, forms monodisperse spheroidal aggregates, is electron dense, and has the property of anomalously scattering x-rays at specific wavelengths. All these properties combined make gold an optimal metal to be “visualized”. In her most recent application of gold, in press in the journal Structure, Kelsey collaborated with a group at the University of Osnabruek in Germany in the synthesis of a reagent conjugated with monodisperse gold clusters or nanoparticles (called AuNPtris-NTA, see figure) and employed this reagent to localize protein(s) of interest in large multi-protein assemblies.
The experiment most visually striking to demonstrate the utility of this new “gold reagent” involved attaching it to a protein that interacts with itself to form a ring shaped structure. When visualized using the electron microscope, the gold clusters or nanoparticles site-specifically attached to the protein appear as extremely dense black spots due to their significant scattering of electrons as a consequence of the gold’s electron dense structure.
In essence, Kelsey has created a stunning golden microscopic studded ring. Next up, employing this gold conjugated reagent in other new ways.
See: Anthony et al., High-Affinity Gold Nanoparticle Pin to Label and Localize Histidine-Tagged Protein in Macromolecular Assemblies, Structure (2014)
Bring your research and entrepreneurial ambitions to life!
The Brandeis University Virtual Incubator invites member of the Brandeis Community (undergrads, grad students, postdoctoral fellows, faculty, staff) to submit an application for a “Sprout Grant”. These grants are intended to stimulate entrepreneurship on campus and help researchers launch their ideas and inventions from Brandeis to the marketplace.
This spring we will be awarding $50,000 to be shared amongst the most promising proposals.
Come get your questions about the Sprout grant answered at one of our upcoming information sessions.
Tuesday February 18th 1pm – 2pm
Tuesday February 25th 10am – 11am
Thursday February 27th 11am – noon
Tuesday March 4th 11am – noon
All information sessions will be held in the Shapiro science center 1st floor library, room 1-03 (the glass walled room near the elevators).
Deadlines: Preliminary applications are due on Friday, March 7th
Benefits of participation:
- Teams that are selected to submit full applications will be given assistance in further developing their ideas into an effective business pitch.
- Sprout grant winners will be connected with an experienced mentor, and given further assistance in getting their ideas to market by the Office of Technology Licensing.
- Previous winners have come from many departments: Neuroscience, Biology, Biochemistry, Physics and Computer Science. Some of the funded technologies have resulted in patent applications and are moving towards commercial development. Read more about previous winners from your department here: Sprout winners 2011, Sprout winners 2012, Sprout winners 2013.
The Department of Biochemistry at Brandeis University invites applications for a tenure-track faculty position, to begin Fall 2014. We are searching for a creative scientist who will establish an independent research program and who in addition will maintain a strong interest in teaching Biochemistry at the undergraduate and graduate levels. The research program should address fundamental questions of biological, biochemical, or biophysical mechanism. Brandeis University offers the rare combination of a vigorous research institution in a liberal-arts college setting. The suburban campus is located 20 minutes from Boston and Cambridge and is part of the vibrant community of academic and biotechnology centers in the Boston area. The application should include a cover letter, curriculum vitae, statement of research accomplishments and future plans, copies of relevant publications, and three letters of reference. Applications will be accepted only through AcademicJobsOnline at https://academicjobsonline.org/ajo/jobs/3366. Additional inquiries may be directed to Dan Oprian, Professor of Biochemistry (email@example.com). First consideration will be given to applications received by December 1, 2013.
Brandeis University is an Equal Opportunity Employer, committed to building a culturally diverse intellectual community. We particularly welcome applications from women and minority candidates.
Fluoride anion is everywhere. Released into water through the natural weathering of rocks, it’s present to the tune of 5 mM in toothpaste, 30 μM in Cape Cod bay, and 17 μM in Massell pond at Brandeis.
Since F– is ancient, ubiquitous and toxic to microbes, it’s not surprising that bacteria have evolved defenses to expel it from their cytoplasm. In an article published in eLife on August 27, 2013, Randy Stockbridge, Janice Robertson, and Luci Partensky from Chris Miller’s lab describe one of these microbial defenses, a fluoride channel called Fluc. The channel provides a pathway for F– to exit the cell across the membrane at a rate of 107 ions per second, while rigorously excluding Cl– in order to avoid catastrophic membrane depolarization. The world-record 10,000-fold selectivity isn’t the only remarkable aspect of Fluc, however. The Fluc channel is built on an antiparallel dimer scaffold, with one of the subunits facing the exterior of the cell, and the other facing the interior. Only one other modern-day membrane protein is known to dimerize like this, but the arrangement recalls the inverted structural repeats that are a common, important motif for membrane transporters. Inverted repeats are the product of an antiparallel dimer, like Fluc, that duplicated and fused eons ago. The sequences drifted over time until the duplication was undetectable by sequence similarity, and the plethora of membrane transport proteins built on this plan was only discovered when the 3-D structures were solved. The Fluc family provides the opportunity to study microorganism resistance to an ancient xenobiotic, as well as membrane protein architecture from an evolutionary origin.
For more, you should read the paper:
PS: If you’re wondering about the tea on the bar graph, tea plants accumulate F– in their leaves. Cheap teas, made from older tea leaves, actually carry a lot of F–, and if you drink a couple quarts of lousy tea a day, you can give yourself skeletal fluorosis.
Winners of the 2013 Sprout Grant competition held by the Brandeis Office of Technology and Licensing have been announced. Sprout grants support research that is “novel, patentable and [has] commercial potential“, and encourage students to think about new and different ways to apply their basic science for practical good. Each team applying for a grant must be led by a Brandeis student or postdoc (noted in asterisks below), who were responsible for presenting their proposals to the review panel.
Teams that received funding.
- Marcus Long (*), Ann Lawson, Lior Rozhansky ’15, and Liz Hedstrom: $20,000 to develop novel inhibitors of deubiquitinating enzymes;
- Michael Heymann (*), Achini Opathalage, Dongshin Kim, and Seth Fraden: $5,500 for its development of CrystalChip;
- Michael Spellberg (*), Calla Olson, Marissa Donovan, and Mike Marr: $10,000 to develop a tool to purify Calmodulin-tagged recombinant proteins;
- Julian Eskin (*) and Bruce Goode: $2,000 for work on a rapid and efficient kit to purify actin;
- Eugene Goncharov ’13 (*), Yuval Galor ’15, and Alex Bardasu ’15: $2,500 towards development of their iPhone app LineSaver, which collects data on local hotspots and gives users an estimated wait-time for restaurants, clubs and tourist attractions.
You can read more at BrandeisNOW
The Biochemistry Department is delighted to announce that Timothy Street has accepted a position as Assistant Professor of Biochemistry. He will arrive at Brandeis in early September.
Timo received his undergraduate degree in Physics from UC Berkeley and his PhD in Biophysics from Johns Hopkins. For the past few years he has been carrying out postdoctoral research at UCSF in the lab of David Agard. He works at the nexus of structural biology and the physical chemistry of protein folding, focusing on a perplexing, challenging class of “molecular chaperones,” proteins that help other proteins fold properly into their native conformations. One of the great puzzles in this biologically crucial field is how these chaperones recognize and engage with the proteins emerging from the ribosome that are improperly folded and need their energy-dependent attention. Moreover, this process is intimately related to the unfolded protein response, a kind of cellular panic-button. To attack these kinds of questions, Timo applies a wide range of structural and kinetics methods and in his postdoctoral work has shown how these may be cleverly integrated to picture the mechanisms of highly dynamic chaperone proteins. He is beginning new projects to develop sensors that will allow him to dissect the actions of chaperones in live cells, to complement the mechanistic pictures emerging from his in vitro studies in purified, defined systems.
To utilize the information contained within a cell’s genes, the enzyme RNA polymerase must find the beginning of each gene (the promoter). Finding the beginning is a prodigious task: RNAP must start at a particular base pair of DNA, but the cell contains millions of base pairs to choose from. It has been proposed that gene-finding challenge is aided by a process termed ‘facilitated diffusion’ (FD). In FD, RNA polymerase first binds to a random position on DNA and then slides along the DNA like a bead on a string until it encounters the target DNA sequence.
In a recently published study in PNAS (1), biophysicists Larry Friedman and Jeffrey Mumm worked with Prof. Jeff Gelles in the Brandeis Biochemistry department to test key predictions of the FD model. They used a novel light microscope that Friedman and colleagues invented and built at Brandeis, a microscope that can directly observe the binding of an individual RNA polymerase to a single DNA. The scientists studied the σ54 RNA polymerase holoenzyme, an RNA polymerase found in most species of bacteria. Surprisingly, none of the three predictions of the FD model that the experiments tested were found to be valid, demonstrating that target finding by the polymerase is not accelerated by sliding along DNA. Friedman and colleagues instead propose that RNA polymerases are present in such large numbers that they can diffuse through the cell and efficiently bind to their target sites directly. The absence of FD may explain how other proteins can bind to positions on the DNA that flank gene start sites and yet not interfere with RNA polymerase finding the gene.
Is this the end of the story? Not likely, given previous publications suggesting FD plays a role for some other DNA binding proteins. Using single-molecule techniques like those developed in the Gelles lab, scientists in next few years should give us a better idea if FD is very rare or very common. [editor: as a chemical engineer, I’m sad to see FD not have a role — it seemed like such a nice theory…]
Friedman LJ, Mumm JP, Gelles J. RNA polymerase approaches its promoter without long-range sliding along DNA. Proc Natl Acad Sci U S A. 2013 May 29. [Epub ahead of print]