Cancer Drug Candidate Leads to Proteomics Method

Scientists at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical have devised an affinity capture-based proteomics technique that could be used to identify and map dysregulated protein pathways in a number of different cancers.

The technique, which was detailed in a paper published Nature Chemical Biology, relies on the inhibitor PU-H71 – a small molecule that selectively binds tumor-enriched Hsp90 proteins, enabling pulldown of Hsp90-bound oncogenic client proteins. According to MSK researcher Gabriela Chiosis ― one of the developers of the method ― measurement of these captured proteins combined with bioinformatic analysis could provide a better understanding of tumor biology.

Sox17 Gene Key to Pathway to Myelination

Through the identification of a gene’s impact on a signaling pathway, scientists at Children’s National Medical Center continue to make progress in understanding the mechanics of a key brain developmental process: growth and repair of white matter, known as myelination. The study, published online in the September 2011online edition of The Journal of Neuroscience, identified Sox17 as the gene that helps regulate the Wnt/beta-catenin signaling pathway during the transition of oligodendrocyte progenitor cells, or immature brain cells, to a more mature, differentiated state where they generate myelin.

Recommended Readings: Mary Beth Hatten Ph.D. Monday October 3, 2011

Monday Seminar Series

New Directions in CNS Migration

Mary Beth Hatten  Ph.D.

Laboratory of Developmental Neuroscience

Monday, October 3, 2011,  4 p.m.,  Caspary Hall

 

Recommended Reading:

Schneider S; Gulacs A; Hatten ME.  2011.  Lrp12/Mig13a reveals changing patterns of preplate neuronal polarity during corticogenesis that are absent in reeler mutant mice.    Cerebral Cortex.  21(1):134-144.

Aboitiz, F; Montiel J; Garcia RR.  2005.   Ancestry of the mammalian preplate and its derivatives: evolutionary relicts or embruonic adaptations?  Rev Neuroscience  16(4):359-376.  Request from Markus Library.

Kondos SC; Halfaludi C; Voskoboinik I; et al.  2010.  The structure and function of mammalian membrane-attack complex/perforin-like proteins.  Tissue Antigens.  76(5):341-351.

Wilson Perrin M; Fryer RH; Fang Y; et al. 2010.  Astn2, a novel member of the astrotactin gene family, regulates the trafficking of ASTN1 during clial-guided neuronal migration.   Journal of Neuroscience    30(25):8529-8540

Govek EE; Hatten MB; Van Aelst L.   2011. The role of Rho GTPase Proteins in CNS Neuronal Migration.   Developmental Neurobiology.  71(6, Sp. 1): 528- 553.

Antonia Baltrons M; Susana Boran M; Pifarre P; et al.  2008.  Regulation and Function of cyclic GMP-mediated pathways in glial cells. NEUROCHEMICAL RESEARCH   33(12):2427-2435 

Structural Biology Lecture Series: Venki Ramakrishnan Ph.D. Wed Sept 28 2011

Structural Biology Lecture Series

The Structural Basis of Decoding by the Ribosome

Dr. Venki Ramakrishnan

2009 Nobelist

Medical Research Council Laboratory of Molecular Biology

Wednesday September 28, 11 am, Caspary Hall

Recommended Readings:

Voorhees RM; Schmeing TM; Kelley AC; Ramakrishnan V. 2010. The mechanism for activation of GTP hydrolysis on the ribosome. Science 330:835-838.

Schmeing TM; Voorhees RM; Kelley AC; et al.  2009. The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA.  Science  326(5953):688-694.

Gao Y-G; Selmer M; Dunham CM; Weixlbaumer A; Kelley AC; Ramakrishnan V. 2009. The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science 326:694-699.

Weixlbaumer A; Hong J; Neubauer C; Voorhees RM; Sabine P; Kelley AC; Ramakrishnan V. 2008. Insights into translational termination from the structure of RF2 bound to the ribosome. Science 322:953-956.

Selmer M; Duham CM; Murphy FV; Weixlbaumer A; Sabine P; Kelley AC; Weir JR; Ramakrishnan V. 2006. Science 313:1935-1942.

Petry S; Brodeson DE; Murphy FV; et al.  2005.  Crystal structures of the ribosome in complex with release factors RF1 and RF2 bound to a cognate stop codon.  Cell  123(7):1255-1266.

Ogle, JM; Murphy FV; Tarry MJ; et al.  2002. Selection of tRNA by the ribosome requires a transition from an open to a closed form.  Cell  111(5):721-732.

Wimberly BT; Brodeson DE; Clemons WM; et al.  Structure of the ribosomal subunit. 2000. NATURE   407(6802): 327-339.

Carter AP; Clemons WM; Broderson DE; et al.  2000.  Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics.  NATURE  407(6802):340-348.

New Open Access Stem Cell-Omics Database

Scientists at the University of Wisconsin-Madison have launched an open-access database for collecting and analyzing quantitative information about pluripotent stem cells, including data on mRNA, protein, and post-translational modifications.

Named the Stem Cell -Omics Repository, the resource was launched this week to coincide with a study published in Nature Methods comparing the proteomes and phosphoproteomes of human embryonic and induced pluripotent stem cells.

In addition to providing this protein-level comparison, the paper lays out a proteomic workflow using a relatively large number of samples and biological replicates to draw out subtle but potentially important differences between similar cell types, said study leader Joshua Coon, UW-Madison assistant professor

For the stem-cell work the researchers “combined high accuracy mass spectrometry and isobaric tagging on a large scale” in a way that let them compare proteins and phosphorylation sites across four ESC lines and four iPSC lines in biological triplicate. This enabled them to identify differences between the lines that would otherwise have gone undetected.

Recommended Readings: Barry S. Coller M.D. Monday Sept 26 2011

Monday Lectures

Combing Structure-Based Design and Mass Screening to Probe

 Ligand Binding to Integrin Receptors

Barry S. Coller  M.D.

Vice President for Medical Affairs and Physician-in-Chief

Laboratory of Blood and Vascular Biology

September 26, 2011,  Caspary Auditorium,  4 p.m.

Recommended Readings

Litvinov RI; Barsegov V; Schissler AJ; Fisher AR; Bennett JS; Weisel JW; Shuman H.  2011.  Dissociation of bimolecular αIIβ3-fibrinogen complex under a constant tensile force.   Biophysical Journal.  100(1):165-73.

Lord MS; Cheng B; McCarthy SJ; et al.  2011.  The modulation of platelet adhesion and activation by chitosan through plasma and extracellular matrix proteins.  Biomaterials. 32(28):6655-6662  (Request from Markus Library)

Blue R; Li JH; Steinberg J; et al.  2010.  Effects of limiting extension at the alpha IIb Genu on ligand binding to integrin alpha IIb beta 2.  Journal of Biological Chemistry.  285(23):17604-17613.

Sheldrake HM; Patterson LH.  2009.  Function and antagonism of beta(3) integrins in the development of cancer therapyCurrent Cancer Drug Targets. 9(4):519-540.  (Request from Markus Library)

Basani RB; Zhu H: Thornton MA: et al.  2009.  Species differences in small molecule binding to alpha IIb beta 3 are the result of sequence difference in 2 loops of the alpha IIb beta propeller.   Blood.  113(4):902-910.

Blue R; Kowalska MA; Hirsch J; et al.  2009.  Structural and therapeutic insights from the species specificity and in vivo antithrombotic activity of a novel alpha IIb beta 3 antagonist. Blood  114(1):195-201

Blue R; Murcia M; Karan C; et al.  2008.  Application of high-throughput screening to identify a novel alpha IIb-specific small-molecule inhibitor of alpha IIb 3-mediated platelet interaction with fibrinogen.  Blood.  111(3):1248-1256.

Hynes, RO.  2002.  Integrins: bidirectional, allosteric signaling machinesCell. 110(6):673-687.

MicroRNA Helps Put Turtles “In Their Place”

A new technique for animal classification could quell the long-running debate between paleontologists and molecular biologists as to where turtles belong on the evolutionary tree. While some camps have argued that turtles are closer to crocodilians and birds, researchers at the Mount Desert Island Biological Laboratory in Bar Harbor, Maine; Dartmouth College; and Harvard University have published data in Biology Letters suggesting that turtles are more closely related to tuataras and lizards. The team identified 77 new microRNA families in the Anolis carolinensis lizard genome, four of which are also expressed in Chrysemys picta bellii, the Western painted turtle, leading them to conclude that turtles and lizards have much more in common than previously thought.

Harvard Says the U.S. Government Got “MyPlate” Wrong For Healthy Eating

The Harvard School of Public Health has a few bones to pick with the federal government’s MyPlate healthful-eating icon.

They’ve aired their differences in the newly released (and not-so-catchily named) “Healthy Eating Plate.” The new plate looks a lot like MyPlate but with revisions and add-ons that its creators argue offer a more accurate picture of what nutritious diet should look like.

A press release announcing the new icon contends that USDA’s MyPlate was cooked up with too much input from powerful agricultural interests, whose influence led to MyPlate’s allowing too much space for dairy, red meat, potatoes and refined grains. By contrast, the press release says, the new plate is based on the latest science .

Meet the 2011 MacArthur Fellows

The MacArthur Fellows Program awards unrestricted fellowships to talented individuals who have shown extraordinary originality and dedication in their creative pursuits and a marked capacity for self-direction. There are three criteria for selection of Fellows: exceptional creativity, promise for important future advances based on a track record of significant accomplishment, and potential for the fellowship to facilitate subsequent creative work.

The MacArthur Fellows Program is intended to encourage people of outstanding talent to pursue their own creative, intellectual, and professional inclinations. In keeping with this purpose, the Foundation awards fellowships directly to individuals rather than through institutions. Recipients may be writers, scientists, artists, social scientists, humanists, teachers, entrepreneurs, or those in other fields, with or without institutional affiliations. They may use their fellowship to advance their expertise, engage in bold new work, or, if they wish, to change fields or alter the direction of their careers. 

Meet this year’s awardees.

Gamers Solve Protein Puzzle That Stumped Science

What has taken researchers more than a decade to chip away it, gamers solved in weeks.   Foldit players have solved the structure of a retroviral protease of the Mason-Pfizer monkey virus; their solution and its validation appear in a paper published online in advance in Nature Structural & Molecular Biology this week. The University of Washington’s David Baker, the Foldit creator, tells Nature‘s News blog that “the M-PMV structure had stumped scientists for a very long time before Foldit players made their breakthrough, adding: “This is the first example I know of game players solving a long-standing scientific problem.”