LMP student seminars: 4 November
Each week during term time, MSc and PhD candidates in the Department of Laboratory Medicine and Pathobiology present their research.
Anyone is welcome. No need to register.
Location: Medical Sciences Building, rooms 4171 or 4279, see below.
As part of the core research curriculum, students taking LMP1001/2/3: Graduate Seminars in Laboratory Medicine and Pathobiology will present their projects. Please see abstracts below.
1. Brain and Neuroscience
James Dunbar
- Title: Developmental Mechanisms of Topographic Map Alignment in the Mammalian Visual System
- Supervisor: Dr. Michael Reber
Matthew David Madrozos
- Title: Developing a Rat Model for the Lewy Body Variant of Alzheimer's Disease
- Supervisor: Dr. JoAnne McLaurin
2. Cancer, Development and Aging
Location: MSB 4171
Adrian Beckett Levine
- Title: TBA
- Supervisor: TBA
Yuetong Song
- Title: TBA
- Supervisor: TBA
Abstracts
James Dunbar: Developmental Mechanisms of Topographic Map Alignment in the Mammalian Visual System
The Ganglion Cell Layer of the retina is comprised primarily of Retinal Ganglion Cells (RGCs), spread evenly across its surface. Each of these RGCs relay visual information deep into target tissues within the brain. The process is tightly organized and regulated, such that axons projecting from RGCs will maintain their arrangement after establishing synaptic connections in the target (i.e., neighbouring termination zones in the target tissue will have neighbouring soma in the source tissue), thus forming a topographic map. The Superior Colliculus (SC) is one such target of topographic mapping and is located in the dorsal midbrain of developing animals. The accessibility of the SC throughout key developmental timepoints makes it an ideal model to study the mechanisms of topographical mapping.
Previous research has shown a class of contact receptors (Eph receptors and ephrin ligands) play an important role in the refinement of these maps during visual development. While constitutive knock-out and knock-in experiments yield only subtle phenotypes, subpopulation-specific modifications to Eph/ephrin signaling driven by Isl2 results in strong mapping phenotypes. In the extreme, maps may be fully duplicated, forming two separate topographic representations of the source tissue. In this project, I will analyze the development of the mammalian visual system through the regulation of Eph/ephrins.
Previous research has demonstrated the constitutive knockouts of ephrin-A2 results in no discernible mapping phenotype in the superior colliculus. However, other mosaic genetic manipulations to Eph/ephrin signalling driven by Isl2 result in strong map duplication phenotypes. Therefore, a novel Cre-Lox mouse line -- Isl2 Cre-EGFP -- was custom-made to drive the expression of Cre in approximately 40-50% of RGCs, scattered uniformly throughout the GCL.
When combined with commercially available floxed ephrin-A2 animals, this system drives a subpopulation specific knockout of ephrin-A2 in RGCs. This conditional-knockout line will be used to probe the mechanisms of topographic mapping in the Superior Colliculus. Fluorescent tracer dyes will be used to visualize the connectivity between the retina and SC, as well as V1 and SC, to explore any map duplication phenotypes.
Based on computational modelling, we predict that the subpopulation specific knockout of ephrin-A2 in the retina driven by Isl2-Cre-EGFP (creating a mosaic genotype in developing RGCs) will lead to a duplication in the Cortico-Collicular Map but not in the Retino-Collicular map in the brains of these animals.
Matthew David Madrozos: Developing a Rat Model for the Lewy Body Variant of Alzheimer's Disease
Alzheimer’s disease (AD) is characterized by the presence of two misfolded proteins, amyloid- b (Ab) peptide and tau. Pathological studies have demonstrated that mixed dementias are more common than pure AD. A -synuclein (a-syn), most commonly associated with Parkinson’s disease, was found in the form of Lewy Bodies or Lewy neurites in autopsied AD brains. There are currently no preclinical models that faithfully recapitulate the pathology found the Lewy body variant of AD (LBV-AD). The aim of this project is to develop a pre-clinical model for LBV-AD. In doing so I hope to elucidate how AD and a-syn pathology interact to produce unique pathological and behavioural phenotypes.
F344TgAD (Tg) and non-transgenic (NTg) littermate rats received a unilateral injection of AAV 2/5 serotype virus containing full length or C-terminally truncated a-synuclein (SYN119), under the synapsin-1 promoter, into the amygdala at nine months of age. The contralateral hemisphere was used as the control. Tissue was collected at three- and five-months post injection for pathological analysis.
Over-expression of both full-length a-syn (hSNCA) and SYN119 produced aggregates within the amygdala. Rats injected with full-length a-syn displayed greater area coverage compared to SYN119 injected rats. There appeared to be no significant difference in glial activation or neuronal loss at three months post-injection. At five months post-injection there was a significant difference in a-syn pathology between Tg and NTg hSNCA injected rats.
This preliminary data indicates that AD pathology influences a-syn pathology in genotype specific and time dependent manner for hSNCA injected rats only.
Adrian Beckett Levine: TBA
TBA
Yuetong Song: TBA
TBA
Contact
No need to register.
Contact lmp.grad@utoronto.ca with any questions