2019 UBC Science Co-op Supervisor Recognition Awards
Published on January 24, 2020
Launched in September 2017, the UBC Science Co-op Employer Recognition Award recognizes Companies and Supervisors who have provided exceptional Co-op work term experiences to our co-op students. The award is based on providing meaningful experiential learning; excellent coaching, guidance, and mentorship; and encouraging opportunities for professional growth.
This year, Laurent Volpon, Research Officer for Katherine Borden (Principal Investigator at IRIC), was honoured with this award.
A potato virus helps uncover a new regulation mode for gene expression
Published on December 13, 2019
To create proteins from the information contained in genes, cells use messenger RNAs, which carry the genetic information to the ribosomes (the translation machinery) where this messenger RNA gets converted into proteins. For this conversion to take place, most RNAs must bind a protein called “eIF4E.” eIF4E recognizes messenger RNAs which have a special modification at the front of the RNA known as a “cap”, which stimulates their movement to the translation machinery and ultimately converts messenger RNA into its active form, protein. The cap structure is a centre piece for RNA regulation and is extremely simple; consisting of a modified nucleotide which interacts with eIF4E at what is known as its “cap-binding site”. It was thought that this is the only way that eIF4E can bind to RNAs and engage the translation machinery to convert mRNA to proteins.
Dr. Borden’s team has shown for the first time that the cap-binding site of eIF4E can be co-opted by a protein (about a hundred times larger than the cap). This viral protein, when directly conjugated to large pieces of RNA, can recruit them to the machinery via binding the cap site of eIF4E and converts these RNAs to protein. Thus, instead of using the nucleotide cap, the virus uses a protein for the same job.Read more...
The discovery is the result of work carried out on VPg, a viral protein that attacks potatoes! By infecting a potato plant, the virus injects hundreds of copies of the VPg protein, many of which are attached to a messenger RNA that the virus hopes to convert into protein in order to make viral proteins that allow the virus to multiply. VPg plays a vital role in the operation by taking the protein-making machinery hostage. It achieves this purpose by engaging eIF4E, a protein so essential to life on Earth that it can be found in both animals and in plants. Dr. Borden’s discovery that a protein, which is structurally different to the cap, can recruit RNA to the protein synthesis machinery has never been observed before. This observation suggests there could be a completely different mechanism to engage this machinery for conversion of RNAs into proteins. Whether this is limited to viral proteins or can occur in uninfected cells remains to be determined.
Having determined the three-dimensional structure of VPg, Dr. Borden’s team hypothesized that human proteins with a similar three-dimensional structure may also engage eIF4E. They searched databases by structural homology and identified a human motor protein, KIF11/EG5, a protein studied extensively by Dr. Benjamin Kwok of IRIC. Up until now, EG5 had no link to eIF4E, but their studies showed that they were right: KIF11/EG5 also binds to the cap-binding site of eIF4E, supporting the notion that this new potential mechanism for the control and engagement of eIF4E could be conserved from plants to humans. This work must now be developed further by Dr. Borden and her team.
Gaining a better understanding of eIF4E regulation mechanisms is of great interest because along with playing a vital role in the cell, this protein is abnormally overexpressed in several cancers where its overabundance contributes to transforming normal cells into cancer cells. In previous work, Dr. Borden’s team, and her collaborators, discovered that eIF4E is a very promising therapeutic target for treating certain leukemias.
Structural studies of the eIF4E-VPg complex reveal a direct competition for capped RNA: Implications for translation. Proc Natl Acad Sci USA. Coutinho de Oliveira L, Volpon L, Rahardjo AK, Osborne MJ, Culjkovic-Kraljacic B, Trahan C, Oeffinger M, Kwok BH, Borden KLB.
The eIF4E factor reveals itself in a new way
Published on May 2, 2019
This discovery made by a team of IRIC Investigators could make its way into cell biology textbooks. The laboratory of Katherine Borden recently published a study in Cell Reports revealing a new role for the eIF4E factor: actively participating in the cleavage of the terminal end of messenger RNAs in order to accelerate their conversion to protein.
Before being used to produce a protein, the information contained in a gene first transits by way of a messenger RNA (mRNA). A multitude of proteins act as mentors for these mRNAs. As soon as they are created in the nucleus, they help them mature, leave the nucleus, and lead them to the ribosome where they will be read and translated into proteins.
The eIF4E factor is one of those proteins and helps approximately 3,500 different types of mRNAs accelerate their march to the ribosome.
To do so, the eIF4E factor modulates the translation of mRNAs by attaching itself to their cap, at the leading end of the mRNAs. It then acts in three ways to accelerate the movement of information: by increasing the translation rate of the mRNA, by increasing its stability in the cytoplasm, and by participating in its export from the nucleus. Katherine Borden’s team discovered a fourth mechanism, completely by chance.
While studying its mRNA export activity, the Borden laboratory discovered that eIF4E drives the production of certain proteins involved in the cleavage of mRNAs, a vital step in mRNA maturation. It also discovered that eIF4E directly binds the protein CPSF3, the enzyme responsible for 3’-end cleavage of mRNAs. Molecular biology experiments then established that eIF4E does not just passively bind mRNAs during the maturation steps of mRNAs in the nucleus, it actively participates in the process.
Because eIF4E is an oncoprotein, understanding its mechanisms of action could accelerate the development of cancer therapies. The IRIC team’s discovery adds an important layer of information to the role of this protein.
By Martin Primeau
Nuclear eIF4E stimulates 3’-end cleavage of target RNAs. Cell Reports. M R Davis, M Delaleau, KLB Borden
Published on August 14, 2018
On August 13th 2018, an announcement was held at the Agora, in the presence of the Honourable Ginette Petitpas Taylor – Minister of Health, to highlight the work of the Canadian Institutes of Health Research (CIHR) recipients.
Katherine Borden and Marc Therrien each received a grant from the CIHR, as part of the 2018 Project Grant Spring competition and the 2017-2018 Foundation Grant competition.
They were both present for the occasion, along with our Chief Executive Officer, Michel Bouvier. The announcement was held by the Minister’s Office, in collaboration with the UdeM’s Communications and Public Relations Office.
We also took the opportunity to organize a tour of the Institute, passing by Kathy’s lab and all the way to the High-Throughput Screening (HTS) core facility where Marc explained the scientific work conducted at the IRIC.
The interest was immediate and various interviews were given to the different media outlets. Both the tour and the announcement, resulted in great media coverage.
La Presse : Ottawa investit 378 millions pour plus de 400 projets de recherche en santé
La Tribune : Plus de 400 projets de recherche en santé reçoivent des fonds du fédéral
Métro : Ottawa injecte 32 M$ pour la recherche à l’Université de Montréal
CTV : Federal government devoting $378 million to medical research
The Gazette : Université de Montréal to get $32 million for research project
The ribavirin in the press
Published on April 11, 2013
Researchers from the University of Montreal and a Canadian pharmaceutical company are launching a clinical trial that aims to treat a form of leukemia by combining a common antiviral drug and standard chemotherapy drugs.
After promising results from a 2009 trial that treated 11 acute myeloid leukemia patients with the common antiviral drug Ribavirin, Dr. Katherine Borden was preparing to start a second clinical trial that combined Ribavirin with low doses of standard chemotherapy drugs...
CTV News : Researchers pairing antiviral, chemotherapy drugs to fight leukemia
Published on May 19, 2009
A commonly used antiviral drug that's already used to fight hepatitis C and HIV could also be used to treat 30 per cent of cancer types, according to a new study conducted on patients in Canada.
Doctors in Montreal tested the antiviral drug ribavirin on 11 patients with acute myeloid leukemia (AML), who had undergone several other treatments that had previously failed.
Nine of the patients saw their conditions improve within a matter of months, with one achieving complete remission and two achieving partial remission, all with few side effects...
CTV News : Antiviral drug becomes promising cancer-fighter