Separating proteins and manipulating live cells using magnetic nanoparticles

Brandeis grad students Yue Pan (Chemistry) and Marcus Long (Biochemistry), together with Professors Lizbeth Hedstrom and Bing Xu, have synthesized novel 6 nm diameter magnetic nanobeads (comparable in size to a globular protein) and used them to separate specific proteins from a cell lysate and manipulate live cells. This work has just appeared online in the journal Chemical Science.

Selectively binding glutathione-S-transferase fusion proteins using
glutathione-decorated iron oxide nanoparticles and down-stream applications

These small, magnetic beads have numerous advantages over larger traditional glutathione-modified beads, including rapid purification, and ultra low non-specific binding. Importantly, both the purified GST and the protein of interest (POI) preserve their innate properties. They also demonstrate that functionalized iron oxide nanoparticles can be used to manipulate live cells. This work  establishes design principles for decorating magnetic nanoparticles that will ultimately should lead to a general and comprehensive platform for studying biological interactions and biological systems using a magnetic force.

Thomas, Epstein to Collaborate with Discovery Museums on Dreyfus Foundation Grant

The Discovery Museums (Acton, MA), in collaboration with Professors Christine Thomas and Irv Epstein (Brandeis chemistry department) and Brandeis’s American Chemical Society Student Affiliates Chapter have received funding from the Camille and Henry Dreyfus Foundation to develop and implement a project called Reaction Station: Adventures for Young Chemists.

Pilot tests of a prototype Reaction Box with students

The project aims to enhance and promote hands-on chemistry experiences for youth in schools and museums. Implementation of the project involves first designing “Reaction Stations,” comprised of large plastic boxes with holes cut out for gloved hand access, and then carrying out educational and experiential programming for children using these Reaction Stations. As children are often enticed by messy, smelly, or otherwise highly-reactive experiments, these portable Reaction Stations (similar in concept to gloveboxes used by members of Professor Thomas’s Lab) will provide a safe way for children to engage in experiments that are often avoided in school or museum settings due to their messy nature.

Denise LeBlanc, Director of Learning Experiences at The Discovery Museums (and also a former research scientist in the Rosenstiel Basic Medical Sciences Research Center on campus), anticipates much success from the Reaction Stations. LeBlanc and Thomas will devise various experiments for children to carry out. Possibilities include: identifying a mystery substance as part of a “crime scene,” testing the pH of common household items, exploring reactivity of everyday chemicals that, at first glance, seem inert, and other experiments that introduce children to topics of polymers, chromatography, phase changes, etc.

Undergraduate students in the American Chemical Society Student Affiliate Chapter will work with the children as model scientists and helpers. Throughout the duration of the year, undergrads from the chemistry department will partake in demonstrations and lessons at the museum in Acton, MA, as well as offsite through various after-school programs. Beyond conducting demonstrations in a museum or school setting only, the Reaction Station will be a teaching tool that educators can bring to their own classrooms or other venues to perpetuate their students’ engagement in chemistry and hands-on research. Says Thomas, “Making research understandable and accessible to children at a young age is pivotal in the development of new generations of chemists.”

The Reaction Station: Adventures for Young Chemists proposal was one of 19 grants awarded this year. Other recipients include universities and museum/science outreach organizations who intend to advance the chemical sciences through innovative projects.

An alternative to scuba diving

Many promising medicinal agents (anti-cancer, anti-bacterial, anti-viral and anti-fungal) have been discovered among the diverse molecules produced by marine organisms. However, scuba-diving to harvest sponges and algae is not usually a practical way of obtaining usable quantities of these compounds, especially if they are present only in trace quantities in the source organisms.

A recently published paper in Organic Letters from the laboratory of Assistant Professor of Chemistry Isaac Krauss is the first to present a synthetic laboratory approach to the preparation of the bromophycolides, originally isolated from Callophycus Serratus, a red algae which was collected off the coast of Fiji. Although these compounds were shown to posses anti-tumour, anti-HIV and anti-malarial properties, algae collected in a second expedition to Fiji apparently contained none of the natural product (hence the desirability of a laboratory synthesis). The bromophycolides are a structurally unique family of natural products containing brominated asymmetric carbon centers and large 19-membered rings. This paper illustrates the preparation of the bromophycolide A and D ring system in high enantiomeric purity via a short (9-step) synthetic sequence.

Thomas named 2011 Sloan Research Fellow

Assistant Professor of Chemistry Christine Thomas has been named a 2011 Sloan Research Fellow. These two-year fellowships are awarded to early-career scientists in recognition of distinguished performance and a unique potential to make substantial contributions to their field. Research in the Thomas laboratory focuses on the design and synthesis of new transition metal complexes to examine the fundamental interactions between different components of bifunctional catalysts with the ultimate goal of uncovering new transition-metal catalyzed bond activation processes related to renewable energy. Since starting in the Chemistry department at Brandeis in 2008, Thomas and coworkers have developed a series of bimetallic catalysts that utilize metal-metal interactions to attenuate redox potentials and promote the activation of small molecules such as hydrogen, alkyl halides, and carbon dioxide.

The Thomas lab has an energetic and talented team of researchers

Arne Ekstrom ’96, PhD ’04 and Mikhail Ershov MA ’00 were also named as 2011 Sloan Research Fellows. Ekstrom received a B.A. in Biology and Psychology from Brandeis, and after getting an M.S. at U. Arizona, returned and completed a Ph.D. in Neuroscience here in 2004, working with Michael Kahana. After a postdoc at UCLA, Arne took a position as an Assistant Professor in the Center for Neuroscience at U. California, Davis. His lab studies spatial memory using EEG and fMRI techniques. Ershov came to Brandeis from Moscow State Univ. and received an MA in Math in 2000 bofore going on to Ph.D. work at Yale and a faculty position at U. Virginia. Ershov is being recognized for research contributions to various aspects of group theory.

3-D Turing pattern formation in a chemical reaction system

In a report in this week’s issue of Science, Brandeis professor Irving Epstein, senior research associate Vladimir Vanag and postdoc Tamas Bansagi use tomographic methods, like those employed in a medical CAT scan, but using visible light in this case, to obtain the first three-dimensional images of Turing patterns. These patterns have been proposed as a mechanism for morphogenesis in living systems, perhaps offering an explanation for phenomena like “how the leopard gets its spots” or skeletal structure in developing limbs. .

Commentary: Wired Science

New route to lycopodium alkaloids

The lycopodium alkaloids are a large and extensively studied alkaloid family. Huperzine A (1), the medicinally most significant lycopodine alkaloid as a potential treatment for Alzheimer’s disease, functions as an acetylcholinesterase inhibitor but may have other roles as has been addressed in several recent reviews.  Sauroine (2, 7,8-dihydroxylycopodine), from Huperzia saururus, was reported in 2004 and shown in 2009 to improve memory retention in the step-down test in male Wistar rats, significantly increasing hippocampal plasticity. 7-Hydroxylycopodine (3), from Huperzia serrata, was also reported in 2004 and may have related biological activity.

In their recent Organic Letters paper entitled the Synthesis of (±)-7-Hydroxylycopodine, the Snider lab at Brandeis developed a new general route to these bridgehead hydroxylated lycopodines. They reported a practical six-step synthesis of 7-hydroxylycopodine which makes it readily available for further biological evaluation. The key step of the synthesis is the treatment of bicyclic enol ether 4 with 60% sulfuric acid that affords tricyclic amino alcohol 5, which is further elaborated to 7-hydroxylycopodine (3) in three steps. The application of this route to the synthesis of sauroine (2) is now under investigation.

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