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School of Medicine
Please refer to the TCNP Google Calendar for a comprehensive list of TCNP seminars of interest.
** 2012 REQUEST FOR PROPOSALS **
As of August 1, 2012, the TCNP of Lysine Modification is soliciting proposals for "Midi-Driving Biological Projects" (Midi-DBPs) for our Center's Core 2. Midi-DBPs are intended to fund 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 6-7 mini-DBPs between August 1, 2012 and July 31, 2013. For more information, please read the RFP or contact Dr. Jef Boeke or Dr. Joel Bader by phone or email.
"Special K" News
Dr. Jef D Boeke, our long time "Special K" leader relocates his lab to New York University, Langone Medical Center
**January 1, 2014** In mid-January, Dr. Jef Boeke moved to New York City to assume his new responsibilities as the Founding Director of the Institute for Systems Genetics at New York University Langone Medical Center! He and his group will be affiliated with the NYU Department of Biochemistry and Molecular Pharmacology. Jef was a faculty member in the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine for 28 years! During that time, Jef founded the High Throughput Biology Center (HiT Center) and spear-headed our TCNP "Special K" initiative. Jef will continue to serve as a TCNP Project Leader, but leadership for our Center has been handed over to Dr. Joel Bader. We wish Jef all the best as he undertakes this new and exciting endeavor, and we look forward to continued collaborations with his group, part of which remains at Johns Hopkins.
The 2013 Charles E. Dohme Memorial Symposium Will Honor Our Friend and Colleague, Professor Robert J. Cotter
**November 20, 2013** This year, The Charles E. Dohme Memorial Symposium will mark the one year anniversary of Dr. Robert ("Bob") Cotter's death with talks on “Mass Spectrometry: Past, Present, and Future”. The symposium will take place on the JHUSOM campus in the Vernon B. Mountcastle Auditorium (Preclinical Teaching Building) from 9:00 a.m. – 5:00 p.m. Check back for more information as the date approaches. For now, click here.
Our TCNP congratulates Dr. Jef D. Boeke on his election to the National Academy of Sciences!!
**April 30, 2013** This morning, our lead P.I., Dr. Jef. D. Boeke, was elected to the National Academy of Sciences in recognition of his distinguished and continuing achievements in original research. The NAS is a private, non-profit society of distinguished scholars established by an Act of Congress in 1863. Members are elected by their peers and serve as objective, highly knowledgeable advisors to the U.S. Government in all matters of science and technology. This year (2013), the Academy celebrates its 150th year of service to the nation and excellence in science. Congratulations, Dr. Boeke!! Click here for the story.
Our TCNP Mourns the Loss of Our Colleague, Professor Robert "Bob" J. Cotter
**November 13, 2012** We learned this morning, much to our shock, that our well-loved colleague, Bob Cotter, passed away during the night. Dr. Cotter was a world-reknowned and much honored pioneer in the field of mass spectrometry. His loss will be deeply felt by family, friends and colleagues here at Johns Hopkins, as well as by the greater scientific community. We will post more details as they become available.
Our TCNP Mourns the Loss of Former Colleague Yu-yi Lin
**September 6, 2012** A Memorial Service to celebrate the life of Dr. Yu-yi Lin will be held on September 6, 2012, at 4:00 PM, in the Sheik Zayed Tower Interfaith Chapel at The Johns Hopkins Hospital. If you have a photo or other memento that you would like to share, or if you would like to speak at the Memorial, please send it to us at: email@example.com. There will also be an opportunity at the Memorial to leave a written message for Yu-yi and his family.
**August 8, 2012** It is with great sadness that we acknowledge and grieve the untimely death of our friend and former colleague Dr. Yu-yi Lin. Yu-yi was a Johns Hopkins BCMB graduate student and post-doctoral fellow in Jef Boeke’s lab. He was an outstanding and very productive scientist, who pioneered much of this TCNP’s work on genetic and protein microarray approaches to defining lysine acetyltransferase and deacetylase networks. While at JHU, Yu-yi won a number of awards for his work, including the David Israel Macht Award for young investigators in 2009, for using a protein acetylation microarray to discover that NuA4 regulates cell metabolism and aging. In the same year, Yu-yi set up his own lab at the National Taiwan University College of Medicine in Taipei, where he focused on lysine modification pathways in human cells. Yu-yi leaves behind his wife, Jin-ying Lu, and three young daughters, as well as a multitude of friends and family who miss him very much.
SPECIAL TCNP-Related Workshop:
**October 1, 2 & 3, 2012** Second Annual Workshop Practical Genomics: From Biology to Biostatistics. This workshop is sponsored by the JHU Computational Biology group. It will use a hands-on, problem solving approach to teach scientists to manage and explore high throughput biological data, both microarray and sequencing. Anyone with an interest in the field and some knowledge of either biology or biostatistics is welcome; there are no prerequisites.
**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 firstname.lastname@example.org or visit sigma.com 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.
** 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"
May 19, 2009 Special IBBS/NIH Roadmap Minisymposium
- 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
- September 11-15, 2012 - CSHL Meeting: Epigenetics & Chromatim
- December 15-19, 2012 - ASCB Annual Meeting 2012
- February 19-24, 2013 - Keystone Symposium: Nutrition, Epigenetics & Human Disease
See our IcePick frozen strain & plasmid distribution system prototype in action!
"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).