Biochemistry, University of Toronto

SickKids scientists and collaborators identify structure of key malaria protein with blocking antibody

21 November 2018|

SickKids scientists have taken an important step forward on the path to finding effective biomedical interventions to halt the spread of malaria, a disease that affected an estimated 216 million people worldwide in 2016 alone.

Jean-Philippe Julien, Canada Research Chair in Structural Immunology, Assistant Professor in the Departments of Biochemistry and Immunology at the University of Toronto, and Scientist in the Molecular Medicine program at SickKids, and his colleagues […]

A novel potential approach to treat cancer: Targetting NUAK2 to block oncogenic YAP/TAZ signaling during tumorigenesis

3 October 2018|

Time-lapse imaging of Clover-YAP WT (first movie) and 5SA (second movie) in MDA-MB231 cells. Localization of Clover-YAP WT (wild type) and 5SA (mutant at all five LATS targeting sites) was monitored before and after addition of NUAK2 specific inhibitor, WZ4003. Note that the nuclear signal is gradually lost after addition of WZ4003 in cells expressing YAP-WT but not affected in YAP-5SA. Images were captured every 10 min for 2 hours. […]

Molecular Dynamics of a Blood Group Antigen

Alex Palazzo2024-10-04T12:59:43-04:0018 July 2018|

In a collaborative project started during a sabbatical leave at Oxford, Reinhart Reithmeier and Antreas Kalli (Leeds) used computer simulations to characterize the dynamics of the human red blood cell anion transport protein Band 3 in a complex lipid bilayer.

The study was published on-line July 16^th in PLOS Computational Biology.

The simulations showed that the signalling lipid, PIP₂, binds to specific sites on the Band 3 protein, a hub […]

Dysregulation of the human mitochondrial protease ClpP induces cancer cell death

Alex Palazzo2024-10-04T12:59:43-04:004 July 2018|

Acyldepsipeptides (ADEPs) compounds have bactericidal properties via dysregulating the activity of the highly conserved tetradecameric bacterial ClpP protease. In a recent publication in Cell Chemical Biology, Keith S. Wong and co-authors from the Houry group have reported on the identification of ADEP analogs that are potent dysregulators of the human mitochondrial ClpP (HsClpP). These analogs interact with HsClpP at high affinity, causing the protease to non-specifically degrade model […]

Malaria: Cooperating antibodies enhance immune response

Alex Palazzo2024-10-04T12:59:43-04:0020 June 2018|

Source: Steve Bryson, PhD

Malaria is one of the most inflicting infectious diseases worldwide. Each year, an estimated 200 million people contract malaria and approximately 440,000 people succumb to the infectious disease.

Scientists in the Julien lab at The Hospital for Sick Children (SickKids) and their collaborators at the German Cancer Research Center (DKFZ) in Heidelberg, Germany, have studied how the human immune system combats malaria infections. In this […]

Avoiding catastrophe: Yeast study reveals clues to maintaining genome size

Alex Palazzo2024-10-04T12:59:43-04:0011 June 2018|

By Jovana Drinjakovic

Study reveals an unexpected role for a well- known protein machinery in maintaining the correct DNA content with implications for cancer and other diseases

As cells divide, they must accurately split their DNA between the two daughter cells or risk having an uneven number of chromosomes which can lead to developmental disorders and cancer. A new Donnelly Centre study uncovers how a […]

New Tools for Biofilm Disruption

Alex Palazzo2024-10-04T12:59:43-04:008 June 2018|

Microbial biofilms grow on biotic and abiotic surfaces. The matrix of the biofilm that the pathogen produces protects them from the host immune response and antibiotics. This proposes a major challenge for the treatment of chronic infections. In an article published in Plos Pathogens, Dustin J. Little and Roland Pfoh (Howell lab) and co-authors demonstrate that the C-terminal domain of PgaB is a glycoside hydrolase that can hydrolyze […]

Tipping Cell Signaling Pathways by Salts

Alex Palazzo2024-10-04T12:59:43-04:0011 April 2018|

Mechanistic Insights into Allosteric Regulation of the A_2A Adenosine G protein-Coupled Receptor by Physiological Cations

Libin Ye¹^,², Chris Neale³, Adnan Sljoka⁴, Brent Lyda⁵, Dmitry Pichugin¹^,², Nobuyuki Tsuchimura⁴, Sacha T. Larda¹^,², Régis Pomès^2,6, Angel E. García³, Oliver P. Ernst^2,7, Roger K. Sunahara⁵, R. Scott Prosser¹^,²^,*

In a recent paper appearing in Nature Communications, Libin Ye (Prosser lab) and co-authors reveal the delicate balance between inactive states and activation intermediates by allosteric […]

Structure and Dynamics of Complexes of G Proteins and their Receptors

Alex Palazzo2024-10-04T12:59:43-04:0016 March 2018|

Ned Van Eps in the Ernst laboratory used DEER spectroscopy together with molecular modeling techniques to map the structure of a complex between a G-protein-coupled receptor (GPCR) and its G protein. A paper describing the methodology used for characterizing the binding interface of the rhodopsin–G protein complex has recently been published in PNAS. The authors discovered that the binding mode of G protein subtypes is distinct and key differences suggest […]

Quantification of the yeast proteome

Alex Palazzo2024-10-04T12:59:44-04:0019 January 2018|

The Brown lab, together with Anastasia Baryshnikova at Calico Labs, used computational analyses to normalize and convert 21 yeast protein abundance studies to the intuitive measurement of molecules per cell. They provide precise and accurate abundance measurements for greater than 90% of yeast proteins, making it the most comprehensive quantitation of the yeast proteome, and any eukaryotic cell, to date.

With this unified dataset in hand, comparative and multivariate outlier […]

Single molecule imaging of mRNAs by the Palazzo Lab provides new insight into Protein Synthesis in mammalian cells

Alex Palazzo2024-10-04T12:59:44-04:003 January 2018|

The Palazzo lab, in collaboration with Jeff Chao’s lab at the Friedrich Miescher Institute for Biomedical Research in Basel Switzerland, has resolved a long standing puzzle in how cells use mRNAs to synthesize proteins as detailed in a paper published in the most recent issue of Cell Reports (Single-Molecule Quantification of Translation-Dependent Association of mRNAs with the Endoplasmic Reticulum, Cell Reports 2017, 21: 3740–3753).

Proteins can be divided […]

How RNA decay promotes transcriptional rewiring during DNA replication stress

Alex Palazzo2024-10-04T12:59:44-04:0013 December 2017|

Raphael Loll-Krippleber from the Brown lab describes how yeast cells exposed to DNA replication stress induced by the anti-cancer drug hydroxyurea use RNA decay to reprogram gene expression. Using complementary functional genomics approaches Raphael found that a specific mRNA encoding the transcriptional repressor Yox1 is degraded at P-bodies sites to prevent accumulation of the Yox1 repressor in the nucleus. Up-regulation of YOX1 expression, as observed when P-body function is […]