Trimethoprim decorated beads for magnetically manipulating mammalian cells

Brandeis grad students Yue Pan (Chemistry) and Marcus Long (Biochemistry), together with postdoc Hsin-Chieh Lin and Professors Lizbeth Hedstrom and Bing Xu, have extended their previous work on 6 nm diameter magnetic nanobeads (comparable in size to a globular protein). They’ve shown that when decorated with the ligand trimethoprim, the nanobeads can be used to selectively bind to target E coli DHFR fusion proteins, and in addition can be used to manipulate live cells with a magnetic force. This work entitled “Cell Compatible Trimethoprim (TMP)-Decorated Iron Oxide Nanoparticles Bind Dihydrofolate Reductase (DHFR) for Magnetically Modulating Focal Adhesion of Mammalian Cells” is now online in the Journal of the American Chemical Society (JACS).

These small, magnetic beads are the first example of solid supported trimethoprim and have numerous advantages over larger traditional beads, including rapid purification, and ultra low non-specific binding. It is, however, their ability to affect live cells that is most important. In the paper they first show that Cos-1 and HeLa cells can be incubated with the beads for over 5 days with little cell death. These cells can subsequently be manipulated by transfection. Finally when exposed to a magnetic force, the focal adhesion of bead-treated Cos-1 cells can be manipulated.

See also: recommendation at Faculty of 1000

Sprout Grant Winners 2011

Entrepreneurship is alive and well at Brandeis.

Last week, fourteen teams of Brandeis scientists presented their research to a panel of industry experts to compete for funding from the Brandeis University Virtual Incubator Sprout Grant Program.  The Virtual Incubator seeks to nurture and support entrepreneurial scientists at Brandeis by providing education, mentoring, networking and seed grants to help move their discoveries from the laboratory to the market.

Judges were impressed by the team presentations. The teams ranged from biologists who have projects that could be ready for licensing as early as next year, to computer science / IT entrepreneurship students with a web application that already has 1200 users.

“We were overwhelmed by the phenomenal proposals we received” says Irene Abrams, Associate Provost for Innovation.  “The response was incredible – with only a few weeks notice, 23 teams applied for Sprout Grants and 14 presented their proposals to the panel of judges.  I was impressed by the level of creativity among the applicants, and by the hard work the teams put into the presentations.  We only had $50,000, so we had to turn down many excellent applications, which we would have funded if we had more money.”

The 2011 winning projects are:

  • Generation Of A Rapid And Efficient Protein Knockout System, Lead Scientist:  Erin Jonasson (with Satoshi Yoshida)
  • Identification Of Molecules For Stabilizing DJ-1, A Protein Involved In Parkinson And Alzheimer Diseases. Lead Scientist: Joey Salisbury (with Brian Williams, Ala Nassar, Jeff Agar and Greg Petsko)
  • Targeting Oncogenic Ras For Protein Degradation, A Novel Approach To Therapy. Lead Scientist: Rory Coffey (with Marcus Long, Ruibao Ren, and Liz Hedstrom)
  • Identifying Pharmacological Chaperones that Promote Survival in Mouse Models of ALS, Lead Scientist: Jared Auclair (with Joey Salisbury, Dagmar Ringe, Greg Petsko, and Jeff Agar)
  • A Novel, Low Cost, Highly Sensitive Form Of Suppression PCR, Lead Scientist: Ken Sugino (with Sean O’Toole and Sacha Nelson)
  • Zen.Do, Team: Bill DeRusha, Joshua Silverman, Jason Urton (Computer Science)

see also: Brandeis NOW

Biochemistry Senior Research Talks on April 29

The Department of Biochemistry presents senior research talks by the 2010/2011 Biochemistry Honor and BS/MS Candidates on Friday, April 29, 11:30-1:30pm in Gerstenzang 121.

Benjamin D. Hornstein – BS/MS
Seq A: construction and analysis of mutants
Advisor: Sue Lovett

Marcus R. Kelly– BS/MS
Replacement Matrices for Transmembrane Proteins
Advisor: Douglas Theobald

Yuliya Y. Mints – BS/MS
Inosine Monophosphate Dehydrogenase and Transcription: a mechanism for retinitis pigmentosa?
Advisor: Liz Hedstrom

Sarah Naomi Olsen – BS/MS
Isolation, Purification, and Characterization of (+)-4R-limonene synthase
Advisor: Dan Oprian

Benjamin M. Whitlock – BS/MS
PABPN1 and SKIIP: A putative mechanism for the onset of Oculopharyngeal Muscular Dystrophy
Advisor: Dagmar Ringe

Philip D. Lessans – BS
Developing a Method of Extracting Native U snRNPs from eukaryotic cells using Snurportin 1 constructs
Advisor: Daniel Pomeranz Krummel

Jessica P. Liken – BS
Deletion Library Screen for Enhancers and Suppressors of ALS-associated FUS/TLS Toxicity in Yeast
Advisor: Greg Petsko

Everyone is welcome and encouraged to come. Pizza will be provided.

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.

Hedstrom named AAAS Fellow

Professor of Biology Liz Hedstrom has been named a fellow of the American Association for the Advancement of  Science (story on Brandeis NOW).

BrandeisNOW ran a follow-up profile on Liz. Moral: always ask your undergraduates whether they’ve thought about  going to grad school.

Back to class

2010 Beckman Scholar Philip Braunstein ’12 discusses his research project in the Hedstrom lab at the last class meeting of Organic Chemistry CHEM 25a. Training the scholars in communicating science and improving the visibility of undergraduate research are key components of the Beckman Scholars program.

Photographs by Nathaniel Freedman

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