Biological Chemistry seminar: Gabriel Rosenblum, Weizmann Institute of Science

Thu, 2019-03-07 15:00 - 16:00

Gabriel Rosenblum

Department of Structural Biology

Weizmann Institute of Science


"Observation of Allosteric Signaling Through DNA with Single-Molecule FRET and Cryo-EM"

Gene networks often obey complex dynamics such as pulsing and oscillations that require a nearly binary “on” and ”off” switch in gene activity. At a molecular level, a high cooperativity in the interaction between transcription factors (TFs) and DNA is key for this switch. However, how this cooperativity is achieved is unknown for many systems. We used a combination of cryo-electron microscopy (cryo-EM) and single-molecule fluorescence spectroscopy to unravel the emergence of cooperativity in the interaction between ComK, a bacterial transcription factor from Bacillus subtilis, and its promoter sequence. The promoter contains two binding sites (AT-boxes) that are separated by 18 base pairs (6 nm). Single-molecule FRET experiments show a low cooperativity for the binding to individual AT-boxes whereas the combination of two distant binding sites in the natural promoter boosts cooperativity. Importantly, the boost does not result from interactions between ComK-molecules at the two sites, as revealed by a cryo-EM structure of the ComK-DNA complex. Instead, the results unravel a new allosteric mechanism. Cooperativity between the ComK-binding sites results from an axially transmitted signal through the DNA-structure. Hence, ComK-binding to one site increases the affinity of the 18 base pair distant site. This communication forms a toggle in which complete binding, i.e., the switch from “off” to “on”, is achieved within a narrow ComK concentration range.



Carolyn Hoff Lynch Room

Chemistry Complex


Host:  Barry Cooperman

Biological Chemistry seminar: Yi-Wei Chang, University of Pennsylvania

Thu, 2019-02-14 15:00 - 16:00

Yi-Wei Chang

University of Pennsylvania


"Structural biology in situ by cellular electron cryotomography"

Electron cryotomography (ECT) enables intact cells to be visualized in 3D in an essentially native state to macromolecular (~4 nm) resolution. It has allowed us to visualize the structures of macromolecular machines in their native context inside intact cells. In many cases, such machines cannot be purified intact for in vitro study. In other cases, the function of a structure is lost outside the cell, so that the mechanism can be understood only by observation in situ. In this presentation, I will use bacterial secretion systems as examples to show how ECT can help us to understand important biological processes by doing structural biology directly inside cells.


Carolyn Hoff Lynch Room

Cret, Chemistry Complex

Novartis Lectures (Julien Papillon, Novartis & Anna Pyle, Yale University)

Thu, 2018-11-29 14:00

Dr. Julien Papillon



Prof. Anna Pyle

Yale University

Lynch Lecture Hall
Attached Document: 

Biological Chemistry seminar: Christina Woo, Harvard University

Thu, 2019-04-25 15:00 - 16:00
Carolyn Hoff Lynch Room



"Chemical control of the O-glycoproteome"


Host:  Dr. David Christianson

Biological Chemistry seminar: Ned Wingreen, Princeton University

Thu, 2019-04-18 15:00 - 16:00

Ned Wingreen

Princeton University


Biological Chemistry seminar, Susan Marqusee, University of California, Berkeley

Thu, 2019-04-11 15:00 - 16:00

Carolyn Hoff Lynch Room

"Protein Folding On and Off the Ribosome"

Biological Chemistry seminar, Jake Jaffe, Broad Institute

Thu, 2019-03-28 15:00 - 16:00

Jacob D. Jaffe

The Broad Institute


Lauren Rachel Zeitels Memorial Lecture




"Proteomic Connectivity Maps for Characterization and Targeting of Drugs" 


There has been an explosion of drug development in the kinase inhibitor and epigenetic modulator spaces.  The primary effects of both classes are fundamentally proteomic, altering the landscape of post-translational modifications in cells.  Mass spectrometry-based proteomic assays are uniquely suited to report on the molecular effects of these drugs. We have developed two scalable proteomic assays to this end: the P100 sentinel assay, which broadly reports on a wide range of signaling activities by monitoring a reduced-representation of the phosphoproteome, and the Global Chromatin Profiling assay, which monitors nearly all of the combinations and permutations of histone modifications commonly present in cells.  We generated a first-of-its-kind systematic library resource of proteomic drug signatures in cells. The majority of drugs generated reproducible signatures, but our analyses indicate the difficulty of identifying traditional “biomarkers” of activity that are paradigmatic for drug development. Eschewing biomarkers, we compared signatures using the "connectivity" concept, enabling data integration across cell types and assays, and co-integration of transcriptional signatures. Connectivity among cell types revealed cellular responses that transcended lineage, while connectivity agreement among assays revealed unexpected associations between drugs.  We further leveraged the resource against public data to recognize therapeutic hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. 




Thursday, March 28, 2019

3:00 PM


Carolyn Hoff Lynch Lecture Hall


Host:  Dr. David Christianson

Biological Chemistry seminar: Thomas Pologruto

Thu, 2018-11-15 15:00 - 16:00
Carolyn Hoff Lynch Room

"Introduction to Econophysics"

Biological Chemistry seminar: Andres Finzi, Université de Montreal

Thu, 2018-10-04 16:00 - 17:00

Carolyn Hoff Lynch Room

Note 4:00 start time.

"Identification of a new HIV-1 Env conformation vulnerable to antibody attack"

Host: Dr. Amos Smith

Department of Chemistry

231 S. 34 Street, Philadelphia, PA 19104-6323

215.898.8317 voice | 215.573.2112 fax |

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