Research Highlights

Mapping the molecular chaperone network

4 October 2017|

Rizzolo et al. from the Houry group provided a comprehensive view of molecular chaperone function in the cell through the use of a systematic global integrative network approach based on physical (protein-protein) and genetic (gene-gene or epistatic) interaction mapping. The analysis revealed the presence of a large chaperone functional supercomplex, which was named the NAJ chaperone complex, encompassing Hsp40, Hsp70, Hsp90, CCT and small Hsps. Many chaperones were found […]

SickKids scientists obtain blueprint of molecular target for blood cancer and autoimmune therapies

4 October 2017|

Researchers at The Hospital for Sick Children (SickKids) have been exploring the molecular structure of immune cell components, and how gaining an understanding of their anatomical organization can help develop future targeted therapies for blood cancers and autoimmune diseases. Dr. Jean-Philippe Julien and co-authors, Dr. June Ereño-Orbea and Taylor Sicard provide the details of their study, “Molecular basis of human CD22 function and therapeutic targeting”, published October 2 in […]

How GPCRs use phosphorylation codes for arrestin recruitment

23 August 2017|

DEER spectroscopy by Ned van Eps in the Ernst lab was used to validate the crystal structure of the phosphorylated G-protein-coupled receptor (GPCR) rhodopsin in complex with arrestin. EPR measurements confirmed the location of the C-terminal tail of rhodopsin on a arrestin binding surface in a non-crystallographic environment. GPCRs are among the most important cell surface receptors controlling nearly all of our physiology. Termination of G-protein-mediated signalling by an […]

Bear Lab shows that a new Cystic Fibrosis treatment improves function from a rare CFTR mutation in patient tissue

14 July 2017|

The laboratory of Christine Bear, together with the group of Régis Pomès and collaborators at The Hospital for Sick Children and Proteostasis Therapeutics, used in silico, in vitro and ex vivo techniques to comprehensively understand the consequences of a rare Cystic Fibrosis (CF) disease-causing mutation in the CFTR gene: c.3700 A>G (ΔI1234_R1239), and subsequently develop a novel mechanism-based therapeutic strategy.

Steven Molinski, first author of the study and recent […]

Howell lab deduces the mechanism of type IV pilus motors

5 May 2017|

Howell lab

The type IV pilus is a long and sturdy grappling hook that bacteria use to attach to a surface and then pull themselves closer to the surface. They are important for virulence in many pathogens, including those that cause cholera, gonorrhoea, food-borne diseases, and multi-drug resistant hospital acquired infections. The molecular mechanism of the motors involved in throwing out and pulling […]

New genetic disease discovered by Drs. Aleixo Muise and Walter Kahr

7 April 2017|

Two of Biochemistry’s professors, Drs. Aleixo Muise and Walter Kahr have discovered a brand new genetic disease through their research at the Hospital for Sick Children.

Their research article is published on Nature Communications.

Their story was also highlighted on the Hospital for Sick Children, CBC The National and CBC News Network, and the Globe and Mail websites:

http://www.sickkids.ca/AboutSickKids/Newsroom/Past-News/2017/SickKids-team-identifies-new-disease-solves-medical-mystery.html

http://www.cbc.ca/news/thenational/new-disease-discovered-1.4054061

[…]

Stagljar lab reveals new interactions among GPCRs

16 March 2017|

Using the modified membrane yeast two‐hybrid (MYTH) technology, researchers from the Stagljar lab mapped membrane protein interactions for clinically important G protein coupled receptors (GPCRs).

Read the full story on Faculty of Medicine website.

Read their paper on Molecular Systems Biology.

 

Researchers revisit the role of conformational dynamics and the protein ensemble in catalysis

21 February 2017|

Houry lab identifies a novel regulator of respiratory chain complexes

13 February 2017|

Graphical abstract_120616

An interaction between the respiratory enzyme fumarate reductase (Frd, also known as Complex II) and an ATPase has been identified in E. coli by the Houry lab. The research shows that the RavA ATPase, belonging to a poorly characterized but ubiquitous MoxR family of AAA+ ATPases, associates with the Frd respiratory enzyme through an adaptor, which the group named ViaA. […]

Ernst Lab discover new way to crystallize membrane proteins

7 February 2017|

The laboratory of Dr. Oliver Ernst has used X-ray crystallography to determine the structure of a membrane protein that never left a lipid-bilayer environment (i.e., without the use of conventional detergents). The work, published in Structure and highlighted on the Journal’s cover, was led by postdoctoral fellow Dr. Jana Broecker. Polymer-bounded lipid nanodiscs were used to extract and purify membrane proteins with their surrounding lipids and allowed […]

Ensminger lab discovers a class of bacterial effectors with novel regulatory activities

3 February 2017|

Many bacterial pathogens modulate their hosts through complex arsenals of effector proteins that are injected into host cell during infection. Indeed, the concept that effectors target host proteins and processes to modulate their activities is central to the current molecular understanding of host-pathogen interactions. Legionella pneumophila, the causative agent of a deadly pneumonia known as Legionnaires’ disease, has over 300 effectors, which is the largest known arsenal amongst bacterial pathogens. […]

Lingwood Lab discover new approach to rescue endogenous misfolded proteins

1 February 2017|

Newly made proteins which do not quite achieve the correct 3D shape in the ER are moved to the cell cytoplasm via a specific membrane pore, and broken down. Many disease causing gene mutations e.g. in cystic fibrosis, also result in misfolding of the mutant protein, and its transport though this pore, for cytoplasmic degradation. This pore is hijacked by some bacterial toxins which need to access the cytoplasm to […]