"Special K" News
Hot Papers
Upcoming Scientific Conferences of Interest
IcePick In Action
PTM Humor

Please refer to the TCNP Google Calendar for a comprehensive list of TCNP seminars of interest.

** REQUEST FOR PROPOSALS **

As of January 1, 2011, the TCNP of Lysine Modification is soliciting proposals for "Mini-Driving Biological Projects" (Mini-DBPs) for our Center's Core 2.  Mini-DBPs are intended to fund small pilot projects - ideally done within the TCNP itself - that will enable recipients, possibly together with their TCNP collaborators, to apply for larger scale funding of novel applications of TCNP technologies.  Small-scale funding is available for 4-8 mini-DBPs between January 1, 2011 and July 31, 2011.  For more information, please read the RFP or contact Dr. Jef Boeke.

"Special K" News

**October 10, 2011**  Congratulations to Dr. Heng Zhu's graduate student Crystal Woodard on the successful completion of her Ph.D. thesis research.  Dr. Woodard presented some of her doctoral work in a seminar entitled "PROTEIN MICROARRAY BASED APPROACHES TO DISCOVERING NOVEL SIGNALING PATHWAYS CONTRIBUTING TO CANCER AND VIRAL PATHOGENESIS".  Dr. Woodard has accepted a post-doctoral position in the lab of Dr. Sheila Collins at the Sanford-Burnham Medical Research Institute, where her research will focus on metabolic signaling networks contributing to diabetes and oxidative respiration.

**October 7, 2011**  Sabri Ben-Achour of NPR Station WAMU 88.5 in Washington D.C. interviewed Dr. Jef Boeke regarding his lab's ongoing ventures in the field of synthetic biology.  Read and listen here.  Boeke is spear-heading a project to construct the first fully synthetic version of a simple eukaryotic organism, namely the brewer's yeast Saccharomyces cerevisiae.  A paper describing the design principles and early milestones for this synthetic yeast genome project, called "Sc2.0", recently appeared in Nature.  PubMed Link

Dr. Robert Cotter recently received two honors for his work in the field of mass spectrometry.  The first is the Frank H. Field and Joe L. Franklin Award for Outstanding Achievement in Mass Spectrometry, which was awarded by the American Chemical Society on April 29, 2011, at the 241st ACS Meeting in Anaheim, CA.  This was followed by an all-day Award Symposium at the 242nd ACS Meeting in Denver, CO in August.  The second honor is the ASMS Award for Distinguished Contribution in Mass Spectrometry, given by the American Society for Mass Spectrometry at the 59th ASMS Conference on Mass Spectrometry and Allied Topics on June 6, 2011, in Denver, CO.

**June 8, 2011** TCNP member Dr. Akhilesh Pandey participated in a Science webinar entitled "The Proteomics of Posttranslational Modifications: Unraveling Cellular Signaling Through Mass Spectrometry". This webinar is produced by the Science/AAAS Business Office and sponsored by Cell Signaling Technology.

SPECIAL TCNP-Sponsored Workshop:

** April 26-28, 2011 **  Along with Sigma-Adrich and Agilent, the TCNP of Lysine Modification is pleased to co-sponsor a workshop entitled:  "Deconvolution of Pooled shRNA Library Screens Using Microarray Technology".  Please contact technicalworkshops@sial.com or visit sigma.com/workshop for further information.

Two special TCNP seminars, both open to the public, will be given in conjunction with the shRNA Workshop.

Dr. DAVID ROOT (Broad Institute of MIT & Harvard) will speak about "TBA" on Tuesday, April 26, 2011, at TBA pm, in TBA.

Dr. WILLIAM HAHN (Dana Farber Cancer Institute & Harvard Medical School) will speak about "Project Achilles:  Functional genomics and cancer" on Wednesday, April 27, 2011, at 1:00 pm, in PCTB Mountcastle Auditorium.

2011 All-Hands Meeting:

The most recent NTCNP All-Hands Meeting took place on April 14-15, 2011 in Rockville, MD.  Click here to see the agenda.  Click here to see photos.  If anyone has additional photos from the meeting that they would like to share, please let Pamela Meluh know.

** November 30, 2010 **  Hear Phil Cole talk about his lab's work and recent publication on the hormone ghrelin and its implications for human metabolism on Maryland Morning with Sheilah Kast (WYPR Radio – Baltimore):  The Low Hormone Diet

** REQUEST FOR PROPOSALS **  The TCNP of Lysine Modification is currently soliciting proposals for "Driving Biological Projects" or DBPs which comprise Core 2 of our Center.  Up to two years of funding for projects that leverage Center technologies to better understand complex biological systems and dynamic cellular processes will become available on August 1, 2010.  Applications must be received by midnight EST, July 1, 2010.  For more information, please read the RFP or contact the Director, Dr. Jef Boeke.

**October 5, 2009**  This TCNP heartily congratulates our colleague, Dr. CAROL GREIDER, PhD, on being awarded the 2009 Nobel Prize in Physiology or Medicine by the Royal Swedish Academy of Sciences.  She shares the award with Drs. Elizabeth Blackburn (UCSF) and Jack Szostak (Harvard Medical School) for their pioneering work on the mechanism and regulation of telomere maintenance.   Hopkins Press Release

Interview with Akhilesh Pandey on "Discoveries, Databases & the Sociology of Science"

Photos from the May 19, 2009 Special IBBS/NIH Roadmap Minisymposium

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HOT PAPERS from our TCNP of Lysine Modification

• Lu JY, Lin YY, Sheu JC, Wu JT, Lee FJ, Chen Y, Lin MI, Chiang FT, Tai TY, Berger SL, Zhao Y, Tsai KS, Zhu H, Chuang LM, Boeke JD. (2011). Acetylation of yeast AMPK controls intrinsic aging independently of caloric restriction. Cell. 146, 969-979.  PubMed Link
• Samara NL, Datta AB, Berndsen CE, Zhang X, Yao T, Cohen RE, Wolberger C. (2010). Structural insights into the assembly and function of the SAGA deubiquitinating module. Science 328, 1025-1029.  PubMed Link
• Barnett BP, Hwang Y, Taylor MS, Kirchner H, Pfluger PT, Bernard V, Lin YY, Bowers EM, Mukherjee C, Song WJ, Longo PA, Leahy DJ, Hussain MA, Tschöp MH, Boeke JD, Cole PA. (2010).  Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor.  Science. 330, 1689-1692.  PubMed Link
  
  This paper describes the rational design, synthesis and biological properties of a bisubstrate inhibitor of the ghrelin O-acyltransferase (GOAT) enzyme.  Ghrelin is a peptide hormone that promotes weight gain in vertebrates and its bioactivity requires GOAT-dependent octanylation at Ser3.  Inhibition of GOAT in vivo, which presumably alters ghrelin activity, improves glucose tolerance and reduces weight gain in wild-type mice.  The work suggests that GOAT represents a new clinical target for the treatment of human metabolic disease.
   
• Lin Y-Y, Lu J-Y, Zhang J, Walter W, Dang W, Wan J, Tao S-C, Qian J, Zhao Y, Boeke JD, Berger SL, Zhu H. (2009). Protein acetylation microarray reveals NuA4 controls key metabolic target regulating gluconeogenesis. Cell. 136, 1073-1084.  PubMed Link
  
  A proteome-wide search for nonhistone substrates of the essential nucleosome acetyltransferase of H4 (NuA4) complex was carried out using yeast proteome microarrays.  Among newly identified substrates are many cytoplasmic metabolic enzymes known to respond to extracellular nutrient sources and/or intracellular energy status.  Acetylation of phosphoenolpyruvate carboxykinase (Pck1), the rate-limiting enzyme in gluconeogenesis, turns out to be crucial for its enzymatic activity both in yeast and in human hepatocellular carcinoma (HepG2) cells.  This indicates an unexpected extra-nuclear function of NuA4 in regulating metabolism in addition to its well-known roles in regulating chromatin-related processes, and suggests that the two processes are somehow coupled.  Furthermore, deacetylation of Pck1 by the histone deacetylase Sir2 suggests reveals a connection between gluconeogenesis and chronological life span in yeast.
   
• Dai J, Hyland EM, Yuan DS, Huang H, Bader JS, Boeke JD. (2008). Probing nucleosome function: A highly versatile library of synthetic histone H3 and H4 mutants. Cell. 134, 1066-1078.  PubMed Link
  
  To probe nucleosome function in vivo, Dai and Hyland constructed a yeast library of 486 histone H3 and H4 mutants. The library includes both systematic substitutions and tail deletion alleles, and the design features enable analysis of each mutant either episomally or at the endogenous locus. Moreover, each mutant is tagged with unique molecular barcodes to facilitate phenotypic analysis of complex pools of histone mutants using repurposed microarrays previously designed for analyzing yeast knockout collections. Such phenotypic analysis mapped nucleosome surfaces required for transcriptional silencing, response to genome stress, fitness in a chemostat, and NHEJ. This collection of histone mutants will enable researchers to probe nucleosomal function in response to myriads of growth conditions or genetic alterations and should elucidate cis- and trans-acting signals for lysine modification within the nucleosome. Construction of more H3 and H4 mutants, as well as histone H2A and H2B mutants are underway! A database that documents these mutations and their associated phenotypes can be found here. This mutant collection will soon be available through Open Biosystems!
     
• Guha U, Chaerkady R, Marimuthu A, Patterson AS, Kashyap MK, Harsha HC, Sato M, Bader JS, Lash AE, Minna JD, Pandey A, Varmus HE. (2008). Comparisons of tyrosine phosphorylated proteins in cells expressing lung cancer-specific alleles of EGFR and KRAS. Proc Natl Acad Sci U S A. 105, 14112-14117.  PubMed Link
   
  Quantitative mass spectrometry in combination with SILAC was used to compare the pattern and extent of tyrosine phosphorylation in isogenic cell lines expressing either normal or cancer-specific signaling molecules.
     
• Molina H, Yang Y, Ruch T, Kim JW, Mortensen P, Otto T, Nalli A, Tang QQ, Lane MD, Chaerkady R, Pandey A. (2008). Temporal Profiling of the Adipocyte Proteome during Differentiation Using a Five-Plex SILAC Based Strategy. J Proteome Res. [Epub ahead of print].  PubMed Link
    
• Qi Y, Suhail Y, Lin Y-Y, Boeke JD, Bader JS. (2008). Finding friends and enemies in an enemies-only network: A graph diffusion kernel for predicting novel genetic interactions and co-complex membership from yeast genetic interactions. Genome Res. [Epub ahead of print].  PubMed Link
    
• Evans-Nguyen KM, Tao SC, Zhu H, Cotter RJ. (2008). Protein arrays on patterned porous gold substrates interrogated with mass spectrometry: detection of peptides in plasma. Anal Chem.  80(5), 1448-1458.  PubMed Link
     
• Ben-Aroya S, Coombes C, Kwok T, O'Donnell KA, Boeke JD, Hieter P. (2008). Toward a comprehensive temperature-sensitive mutant repository of the essential genes of Saccharomyces cerevisiae. Mol Cell. 30(2), 248-258.  PubMed Link
    
• Lin Y-Y, Qi Y, Lu J-Y, Pan X, Yuan DS, Zhao Y, Bader JS, Boeke JD. (2008). A comprehensive synthetic genetic interaction network governing yeast histone acetylation and deacetylation. Genes Dev. 22(15), 2062-74.  PubMed Link
    
• Chen CS, Korobkova E, Chen H, Zhu J, Jian X, Tao SC, He C, Zhu H. (2008). A proteome chip approach reveals new DNA damage recognition activities in Escherichia coli. Nat Methods. 5(1), 69-74.  PubMed Link
    
• Lu J-Y, Lin Y-Y, Tao S-C, Zhu J, Pickart CM, Qian J, Zhu H. (2008). Functional dissection of a HECT ubiquitin E3 ligase. Mol Cell Proteomics. 7, 35-45.  PubMed Link
   
  The authors used a combination of yeast proteome chip assays, genetic screening, and in vitro/in vivo biochemical analyses to identify and characterize eight novel in vivo substrates of the yeast ubiquitylating enzyme Rsp5, a homolog of the human ubiquitin-ligating enzyme Nedd4. This work illustrates how proteome chips can be used to define probable in vivo substrates of lysine modifying enzymes.
    
• Yang M, Culhane JC, Szewczuk LM, Gocke CB, Brautigam CA, Tomchick DR, Machius M, Cole PA, Yu H. (2007). Structural basis of histone demethylation by LSD1 revealed by suicide inactivation. Nat Struct Mol Biol. 14, 535-539.  PubMed Link
    
• Paliwal S, Iglesias PA, Campbell K, Hilioti Z, Groisman A, Levchenko A. (2007). MAPK-mediated bimodal gene expression and adaptive gradient sensing in yeast. Nature. 446, 46-51.  PubMed Link
   
• Pan X, Ye P, Yuan DS, Wang X, Bader JS, Boeke JD. (2006). A DNA integrity network in the yeast Saccharomyces cerevisiae. Cell. 124, 1069-1081.  PubMed Link
   
  Global patterns of synthetic lethal genetic interactions defined 16 functional modules within the genetic network governing DNA integrity in budding yeast. Modules or genes involved in DNA replication, DNA replication checkpoint signaling, and oxidative stress response were shown to be the major guardians against intrinsic DNA damage. In addition, new regulators of mitotic DNA replication and genomic stability were identified. This work provided rich data for further study of genome integrity and validated the development and use of genetic approaches to study the networks, pathways and dynamics of lysine modification.

HOT PAPERS from the Other TCNPs

Alber F, Dokudovskaya S, Veenhoff LM, Zhang W, Kipper J, Devos D, Suprapto A, Karni-Schmidt O, Williams R, Chait BT, Rout MP, Sali A. (2007). Determining the architectures of macromolecular assemblies. Nature. 450, 683-694.  PubMed Link

Alber F, Dokudovskaya S, Veenhoff LM, Zhang W, Kipper J, Devos D, Suprapto A, Karni-Schmidt O, Williams R, Chait BT, Sali A, Rout MP. (2007). The molecular architecture of the nuclear pore complex. Nature. 450, 695-701.  PubMed Link

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Upcoming Scientific Conferences of "Special K" Interest

• January 10-15, 2011 - Keystone Symposium:  Histone Code:  Fact or Fiction
• January 23-28, 2011 - Keystone Symposium:  The Evolution of Protein Phosphorylation
• February 17-21, 2011 - AAAS Annual Meeting
• March 20-25, 2011 - Keystone Symposium:  Mechanism & Biology of Silencing
• March 22-26, 2011 - CSHL Meeting:  Systems Biology:  Networks
• April 9-13, 2011 - ASBMB Annual Meeting
• May 8-13, 2011 - Keystone Symposium: Omics Meets Cell Biology
• May 17-21, 2011 - CSHL Meeting:  The Ubiquitin Family
• June 26-July 1, 2011 - FASEB SRC:  Histone Deacetylases & Reversible Acetylation in Signaling & Disease
• July 10-15, 2011 - GRC:  Chromosome Dynamics
• July 22-24, 2011 - CSHL Meeting:  Single Cell Analysis
• July 24-29, 2011 - GRC:  Cellular Systems Biology
• July 31-August 4, 2011 - FASEB SRC:  Epigenetics, Chromatin & Transcription
• September 4-?, 2011 - FASEB SRC:  NAD Metabolism & Signaling
• August 3-4, 2011 - Joint Biochemical Society/Wellcome Trust Conference:  From Beads on a String to the Pearls of Regulation:  The Structure & Dynamics of Chromatin
  August 7-12, 2011 - GRC:  Epigenetics:  Mechanisms, Develpment
• August 16-20, 2011 - CSHL Meeting:  Yeast Cell Biology
• November 2-5, 2011 - CSHL Meeting:  Genome Informatics
• December 3-11, 2011 - ASCB 51st Annual Meeting

See our IcePick frozen strain & plasmid distribution system prototype in action!

PTM Humor

"The “Hunt” for rare and exotic histone modifications continues" by Sean Taverna originally appeared in an issue of International Journal of Mass Spectrometry dedicated to Donald Hunt (Taverna SD, Allis CD, Hake SB. (2007). Int J Mass Spectrom. 259, 40–45).

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