Research Highlights

How bacterial invaders are sensed in the gut

25 October 2019|

A new paper in the latest issue of Science describes how the bacterial-sensing proteins, NOD1/2, are recruited to the membranes of our gut cells for them to function to initiate a proper immune response. This involves the addition of a lipid, palmitoyl, to NOD1/2 by the palmitoyl-transferase ZDHHC5. Importantly variants of NOD2 that are associated with Crohn’s disease are unable to be palmitoylated.  This work involved an international collaboration […]

Red Cell Anion Exchanger Makes the Cover of Biophysical Journal

1 October 2019|

Dario De Vecchis, a post-doctoral fellow in the laboratory of Dr. Antreas Kalli at Leeds, University, in a collaborative project with Reinhart Reithmeier used molecular dynamics simulations to build the first atomic scale model of the red cell anion exchanger in a complex lipid bilayer that mimics the native membrane. This work appeared in the latest edition of the Biophyisical Journal.  The modelling revealed the dynamic nature […]

Pai lab visualize the inner workings of an enzyme

27 September 2019|

Researchers from the Emil Pai Lab in collaboration with the Miller Lab (Depts. of Chemistry and Physics, University of Toronto) have pieced together a time-lapse movie revealing all the major steps during the catalytic cycle of an enzyme. This study, published in Science, is the most detailed depiction of such a process to date.

The communication between the protein units is accomplished via a water-network somewhat akin to a […]

Enzymatic Activity Regulated by Phase Separation

24 August 2019|

In the latest issue of Science the Forman-Kay lab demonstrate that as proteins transition from the bulk solution to a phase separated condensate in a test tube, this regulates their ability to affect translation and deadenylation in the same manner observed in the cell. Partitioning of components of the translational machinery away from the mRNA can block translation while the unique condensate environment can activate deadenylation.

A previous dogma […]

The inaugural Proteostasis Researchers in Canada (PRinCE) symposium

3 July 2019|

The Proteostasis Researchers in Canada (PRinCE) inaugural meeting was held at the University of Toronto on June 10-11, 2019. The aim of this first symposium was to establish a network of researchers working in the field of protein homeostasis in Canada and to promote collaborations between labs working on topics relevant to proteostasis. These include (but are not limited to) protein folding, protein trafficking, protein degradation, and neurodegenerative diseases – […]

Structure of human mitochondrial ClpP protease – drug complex gains cover of Cancer Cell

24 May 2019|

The crystal structure of ClpP protease activated by the experimental Phase 2 anti-cancer drug ONC 201, as determined by graduate student Ondrej Halgas in Emil F. Pai’s lab, was featured on the cover of the current issue (May 13th, 2019) of the journal Cancer Cell. Together with the laboratories of Walid Houry, Aaron Schimmer (Medical Biophysics) and Michael Andreeff (MD Anderson, Texas), they identified ClpP as the […]

The Ion Transporter NKCC1 Links Cell Volume to Cell Mass Regulation by Suppressing mTORC1

15 May 2019|

Wael Demian from the Rotin lab at Sickkids, recently published a Cell Reports paper showing that the ion transporter NKCC1, known to regulate cell volume, forms a complex with the leucine transporter LAT1 and the Gln transporter ASCT2, and regulates mTORC1 activation via LAT1 and growth factors signaling. Thus, the work of Demian, et al. provides a long-sought link between […]

Dr. David Andrews’ latest discovery highlighted

12 April 2019|

By Matthew Pariselli

In a new eLife paper, Dr. David Andrews, a senior scientist at Sunnybrook Research Institute, and his lab show how an interaction between proteins promotes cancer cell survival.

Andrews, who is also a professor in the department of biochemistry at the University of Toronto, discovered that Bim, a pro-cell-death protein, binds to anti-cell-death proteins at two sites, rendering it “double-bolt locked.” Previously, it was thought there was […]

DNA Replication Stress Causes Mutations

4 March 2019|

Grant Brown’s lab at the Donnelly Centre has characterized a new mutagenic ssDNA gap filling pathway in budding yeast. Their findings will be published in the March 7th issue of Molecular Cell.

DNA replication is a fundamental process that occurs before every cell division and must be completed in a timely and accurate fashion. Under normal cellular conditions this reaction is carried out by the highly processive and accurate replicative […]

How to protect Peroxisomes and Mitochondria from Dying

6 February 2019|

The regulation of organelle abundance is critical for cell function and survival; however, the mechanisms responsible are not fully understood. Imbalances in organelle abundance can result in disease states, including Parkinson’s Disease resulting from dysregulated mitochondrial homeostasis. Peroxisome dysregulation also results in disease, most notably the Zellweger’s spectrum disorders. Although first considered to be caused exclusively by reduced peroxisome biogenesis, recently work shows that the most are due to increase […]

SickKids-led team discovers a drug that disarms a deadly hospital superbug

7 December 2018|

In a new study that was published in Nature Communications, a team led by Roman Melnyk, Associate Professor in the Department of Biochemistry at the University of Toronto and Senior Scientist in the Molecular Medicine program at SickKids, screened thousands of small-molecule drugs to find any that might block the effects of the deadly toxins – without affecting the gut bacteria. Niclosamide, a drug that was approved decades […]

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 […]