Seminars

Fall 2016

The seminars are held on Wednesdays at 12:30pm in the lecture room GB03 in wing B

(Click on the green bar to find out more about the speaker and the topic)

September 20, 2017 - Dr. Michael Levin Univ. of Saskatchewan

The long-term goal of research in the LEVIN LAB is to better understand the cause of neurodegeneration, a salient feature and cause of permanent disability in progressive multiple sclerosis (MS) patients. For more than 20 years, we have studied the function of the RNA binding protein heterogeneous nuclear ribonuclear protein A1 (hnRNP A1 -‘A1’), with a focus on ‘M9’. M9 is A1’s nucleocytoplasmic transport domain, and is required for transport of A1 between the nucleus and cytoplasm. Our lab has discovered that MS patients make antibodies to M9 and the brains and lymphocytes of MS patients contain somatic DNA mutations within M9. Using a number of molecular, in vitro and in vivo techniques, our data indicate that DNA mutations within M9 and autoimmunity to M9 result in A1 dysfunction and subsequent neuronal and axonal degeneration. In this presentation, we will examine potential mechanisms of neurodegeneration resulting from A1 dysfunction.


Michael C. Levin, M.D., is the inaugural SK Multiple Sclerosis Clinical Research Chair and Professor of Neurology & Anatomy-Cell Biology at the U of S. He received his Bachelors of Science degree in chemistry with special honors at the George Washington University and his medical degree at Pennsylvania State University. He attained basic neuroscience training at The Salk Institute. Dr. Levin completed his residency training in neurology at The New York Hospital/Cornell Medical Center – Memorial Sloan Kettering Cancer Center. Drs. Fred Plum and Jerry Posner mentored him during his residency including while he was chief neurology resident. He then completed his multiple sclerosis post-doctoral fellowship in the Neuroimmunology Branch at NIH.

Title: A dysfunctional RNA binding protein contributes to neurodegeneration in multiple sclerosis (MS)

September 27, 2017 - Dr. Vikram Misra, Univ. of Saskatchewan

Several viruses, that appear to cause no overt disease in their natural bat hosts, have spilled over into other mammals causing serious and often fatal disease. These include viruses that cause diseases such as SARS, MERS, Marburg, Ebola, Hendra, Nipah and porcine epidemic diarrhea. An overblown inflammatory response exacerbates the pathology in these diseases. While there are many studies on the interaction of these viruses with their spillover hosts or surrogate laboratory animals, there is little information on the relationship of these or similar viruses with their natural bat hosts. Our objective is to examine the apparently benign relationship between viruses and their natural bat hosts as well as the factors that upset this relationship leading to increased virus replication and, potentially, to spillover to other species. We have identified unique Corona and Herpes viruses that persistently infect most members of two Canadian bat species with no overt signs of illness or pathology. Secondary fungal infections, however, cause an increase in virus replication. We have also discovered that while both bat and human cells react to viral infection with an antiviral response, pro-inflammatory pathways are actively suppressed in bat cells. Our studies will not only provide fundamental information about virus-host relationships in these specialized mammals, but will also give clues about mitigating the serious consequences that often accompany viral spill-over from bats to humans and other species.



Title: Viral spill-over from bats to humans

October 4, 2017 - Dr. Afshin Raouf, Univ. of Manitoba

 

 

Title: Breast tumours induce fibroblast-derived TGFb suppression of progenitor pool in adjacent normal-like tissue

October 11, 2017 - Dr. Maya Shmulevitz, Univ. of Alberta

Reovirus is an enteric virus that is being repurposed into an oncolytic therapy because it prefers to replicate in transformed cells over normal cells. Given that reovirus evolved to thrive in its natural intestinal environment, we wondered what changes to virus and host are required for optimal virus infection in the tumor niche. To address this question, we exposed reovirus to mutagens and used directed evolution to isolate adaptations that favor virus replication in tumor cells.  The unbiased approach revealed several mutations that can promote distinct steps of reovirus replication in tumor cells and promote oncolysis in vivo. The first half of the seminar will discuss examples of virus adaptations that favor reovirus infection of tumor cells. In the second half of the seminar, we will then consider the effects of cellular factors released by tumor cells on extracellular reovirus. In the intestine, reovirus exploits enteric proteases to promote infectivity; but do tumor-associated proteases affect reovirus in positive or negative ways? To address this question, we exposed reovirus to tumor extracellular extracts, and discovered that breast cancer-associated proteases inactivate reovirus. Altogether we propose that oncolytic viruses would benefit from reshaping towards their specific therapeutic niche.

Title: Reshaping oncolytic virus for the tumor niche

October 18, 2017 - Dr. Miroslaw Cygler, Univ. of Saskatchewan

Iron-sulfur (Fe/S) clusters are essential protein cofactors crucial for many cellular functions including DNA maintenance, protein translation, and energy conversion. De novo Fe/S cluster synthesis in mitochondria occurs on the scaffold protein ISCU and requires cysteine desulfurase NFS1, ferredoxin, frataxin, and the eukaryote-specific small factors ISD11 and ACP (acyl carrier protein). Both the mechanism of Fe/S cluster synthesis and function of ISD11-ACP are poorly understood. I will present crystal structures of three different NFS1-ISD11-ACP-ISCU complexes, and describe SAXS analyses to define the 3D architecture of the complete mitochondrial Fe/S cluster biosynthetic complex. The structural and concomitant biochemical studies provide mechanistic insights into Fe/S cluster synthesis at the catalytic center defined by the active-site Cys of NFS1 and conserved Cys, Asp and His residues of ISCU. We further assign specific regulatory rather than catalytic roles to ISD11-ACP that link Fe/S cluster synthesis with mitochondrial lipid synthesis and cellular energy status.

Title: Structural and functional model of the core complex of the eukaryotic Fe/S cluster synthesis machinery

October 25, 2017 - Dr. Jack Gray, Univ. of Saskatchewan

Insects are one of nature’s ideal systems for understanding principles of how animals sense and interact with their environment. They possess tractable nervous systems that evoke and control robust, predictable behaviours. Using traditional and advanced recording techniques, researchers can address fundamental questions regarding sensory processing and coordination of motor outputs that underlie adaptive behaviours. The use of ubiquitous neurotransmitter systems that convey information throughout the insect’s neural circuits further allows us to address questions related to environmental toxicity and how low doses of pesticides affect neural function and behaviour. I will describe experiments in our lab that incorporate these aspects of insects as model systems to address multiple questions. We use the well-described locust flight system to study visual detection of approaching objects and how collision avoidance behaviours are produced. We also study how sub-lethal doses of a neonicotinoid insecticide disrupt visual motion detection an impair avoidance behaviour.

Title: Insights from a tiny mind: Fundamental and practical insect neurobiology

November 1, 2017 - Dr. Joseph Rubin, Univ. of Saskatchewan

Title: TBD

November 15, 2017 - Dr. Dennis J. Thiele, Duke University

Title: TBD

November 22, 2017 - Dr. Deborah Anderson, Univ. of Saskatchewan

Title: TBD

November 29, 2017 - Dr. Sylvia van der Hurk, Univ. of Saskatchewan

Title: TBD

December 6, 2017 - Dr. Eric Yen, Univ. of Wisconsin-Madison

Title: TBD

January 10, 2018 - Dr. John Aitchison, Inst. System Biology, Seattle

Title: TBD

January 17, 2018 - Dr. Brenda Bass, Univ. of Utah

Title: TBD