MSc Exit Seminar - Amber Azam (Zovkic lab)
MSc Exit Seminar
Tuesday, July 25, 2017 at 1:00 pm, DV3129- University of Toronto at Mississauga
Amber Azam (Zovkic lab)
“Genome-wide Characterization of Learning- and Age-related Regulation of the Histone Variant H2A.Z”
Abstract
Histone variants were recently identified as novel regulators of memory, but little is known about their function in the brain. Here, I used next-generation sequencing to characterize genome-wide learning- and age-dependent binding of the histone variant H2A.Z in the hippocampus of young and aged mice. At baseline, H2A.Z co-localized with histone modifications indicative of active transcription and its binding levels were positively correlated with basal gene expression. In response to learning, H2A.Z was widely evicted from ~3000 sites in both young and aged mice, but this eviction was minimally correlated with learning-induced gene activity at both ages. In addition, several age differences were observed. Specifically, H2A.Z levels were higher in aged compared to young mice, suggesting that H2A.Z accumulates with age. Moreover, H2A.Z was evicted from a unique set of genes in aged mice, which also had a distinct gene expression profile compared to young mice.
MSc Exit Seminar - Ola Michalec (Lovejoy lab)
MSc Exit Seminar
Tuesday May 16th, 1:10 pm - Ramsay Wright Building, Rm. 432
Ola Michalec (Lovejoy lab)
"Teneurin C-terminal Associated Peptides (TCAPs): Evolutionary Origins and the Role of TCAP-1 on Calcium Flux in Astrocyte Monocultures and in Astrocytes Co-cultured with Neurons"
Abstract
Teneurin C-terminal associated peptides (TCAPs) are a family of 40-41 amino acid peptides located at the C-terminus of each of the four teneurin type-II transmembrane proteins. The teneurin-TCAP system is ancient and likely arose as a result of a horizontal gene transfer event. TCAPs share sequence similarity to the Secretin superfamily, a less evolutionarily ancient family that includes corticotropin-releasing factor (CRF). The phylogenetic position of TCAP places it as an ancestor of the Secretin superfamily. Calcium ion signaling is integral to all living organisms and astrocytes are integral to the development of the central nervous system in chordates. It is likely that TCAP played a role in these mechanisms. TCAP-1 stimulated calcium signaling in astrocytes but not in astrocytes co-cultured with neurons. This effect is mediated, in part, by the glutamatergic system. Therefore, the ancestral peptide TCAP-1 plays a role in regulating calcium flux in astrocytes.
Ramsay Wright is a wheelchair accessible building.
MSc Exit Seminar - Ashley Miles (Buck lab)
MSc Exit Seminar
Monday April 3rd, 10:10 am - Ramsay Wright Building, Rm. 432
Ashley Miles (Buck lab)
"The inhibitory role of taurine through glycine and GABAA receptors in the anoxia-tolerant western painted turtle brain (Chrysemys picta bellii)"
Abstract
Unlike the anoxia-intolerant mammalian brain, the western painted turtle Chrysemys picta bellii can survive extended periods of anoxia without apparent neuronal damage. This is partly accomplished by a large increase in the levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), resulting in suppression of spontaneous electrical activity (i.e. spike arrest) via shunting inhibition and a decrease in ATP-consumption. Additionally, taurine levels increase, but its function within the anoxic turtle brain is unknown. It is speculated that taurine can function like an inhibitory neurotransmitter, acting through glycine and/or GABAA/B receptors. Given the important role of inhibition in anoxia-tolerance, we wanted to investigate the possible role of taurine as an inhibitory molecule in the anoxia tolerant western painted turtle brain. Using the whole cell patch clamp technique, we measured the response of neurons to taurine. We found that taurine caused the membrane potential of neurons to depolarize approximately 8mV, similar to the effects of the other inhibitory molecules, GABA and glycine, and mimicking anoxia. Additionally taurine increased whole cell conductance >2-fold and induced a current consistent with an efflux of Cl- ions. Compared to GABA and glycine application however, recovery from taurine application was significantly slower indicating a difference in kinetics and possibly a difference in mechanisms of actions. To test the receptor(s) taurine could be acting through to mediate its effects, we used a number of pharmacological inhibitors. We found that taurine’s effects were reduced when the glycine antagonist, strychnine, and the GABAA receptor blockers, gabazine, bicuculline and picrotoxin, were applied but not when GABAB or glutamatergic receptors were inhibited, indicating that taurine activates glycine and GABAA receptors to mediate its effects. Together these results suggest that taurine acts through both glycine and GABAA receptors to affect turtle cortical neurons and therefore may act as an inhibitory signaling molecule during anoxia in the turtle cortex.
Ramsay Wright is a wheelchair accessible building.
MSc Exit Seminar - Dillon McKenna (Peever lab)
MSc Exit Seminar
Thursday January 12th, 12:10 pm – Earth Sciences Centre, Rm. 3087
Dillon McKenna (Peever lab)
"Transduction of human alpha synuclein in the subcoeruleus region causes symptoms of REM sleep behaviour disorder in mice"
Abstract
During rapid eye movement (REM) sleep, vivid dreams and wake-like cortical activity are accompanied by skeletal muscle paralysis (atonia) interspersed with phasic twitches. The motor characteristics of REM sleep are thought to be controlled by the pontine subcoeruleus (SubC) region. REM sleep behaviour disorder (RBD) is a disruption of motor control during REM sleep, which manifests as a loss of atonia, increased phasic twitches, and overt movements. Understanding the development of RBD is vital, as >90% of RBD patients eventually develop some form of synucleinopathy, a neurodegenerative disorder associated with toxic aggregates of the protein alpha-synuclein (αSyn), most commonly Parkinson’s disease. While the brains of RBD patients show αsyn aggregates within the SubC region, there is currently no direct evidence of the effects that SubC αSyn-related pathology will have on the characteristics of REM sleep. Using targeted overexpression of human αSyn in the SubC region, I have demonstrated αSyn aggregation, excessive muscle twitches during REM sleep, and slowing of cortical activity arise in wild type mice. This project demonstrates, for the first time, a direct link between the emergence of RBD symptoms and pathological αSyn in the SubC region, and has produced an animal model of RBD that is clinically relevant to the underlying pathology seen in the human disease.
MSc Exit Seminar - James Colapinto (Berleth lab)
MSc Exit Seminar
Wednesday January 11th, 10:10 am – Earth Sciences Centre, Rm. 3087
James Colapinto (Berleth lab)
" Cis-regulatory Elements Controlling Expression of the Auxin Response Factor MONOPTEROS and its Irrepressible Variant MPΔ"
Abstract
The AUXIN RESPONSE FACTORS (ARFs) mediate changes in gene expression that are associated with auxin response in plants. One of the best-characterized ARFs is ARF5/MONOPTEROS(MP), for which strong loss-of-function and gain-of-function associated defects have been reported. Recent evidence has indicated that auxin response may be driven in part by MP-mediated control of its own expression. Here it is shown that removal of individual ARF-binding auxin response elements (AuxREs) from the MP promoter results in differential expression in specific tissues, while creation of supernumerary AuxREs is associated with auxin response-related phenotypic changes. The irrepressible MP variant MPΔ was used to track potentially expression-stage specific regions of the MP promoter and to determine in which tissues MPΔ can exert its gain-of-function effects independent of the activity of other, closely related ARFs.
MSc Exit Seminar - Mathieu Poirier (Harrison lab)
MSc Exit Seminar
Friday January 6th, 2:10 pm – Room SW 403, University of Toronto at Scarborough
Mathieu Poirier (Harrison lab)
"Characterization of F-actin flashes on phagosomes in macrophages"
Abstract
Macrophages are specialised leukocytes tasked with the engulfment and destruction of foreign particles. We are studying particle uptake by the CR3 receptor in macrophages. Post particle internalization, we have shown that F-actin localizes transiently at phagosome membranes and this event, termed F-actin flashing, often results in red blood cell deformation, lysis and occasionally fission, suggestive of a force-generating property. Putative mechanosensing properties were also proposed based on identification of certain phagosome membrane-localized proteins, as well as distinctions in temporal dynamics based on the internalized particle’s malleability. We have also reported that certain stages of maturation were delayed in phagosomes exhibiting F-actin flashing. Finally, inhibiting myosin IIA activity significantly reduced the frequency at which red blood cell-containing phagosomes became deformed simultaneously with transient F-actin accumulation. Actomyosin-driven contractions could serve to physically distort malleable particles, akin to “chewing”, which may have implications in phagosome maturation, as well as antigen presentation.
MSc Exit Seminar - Mitchell Li Cheong Man (Moses lab)
MSc Exit Seminar
Tuesday December 20th, 2:10 pm – Earth Sciences Centre, Rm. 3087
Mitchell Li Cheong Man (Moses lab)
"Functional Analysis of Short Linear Motifs in Intrinsically Disordered Regions"
Abstract
Short linear motifs (SLiMs) are regulatory binding sites that are involved in signalling and protein regulation. SLiMs are often found in intrinsically disordered regions (IDRs) which are rapidly evolving regions that do not adopt stable tertiary conformations. Despite their prevalence throughout the proteome, many SLiMs still remain unknown. Predicting novel SLiMs, determining their function, understanding how they cooperate and evolved are ongoing endeavours.
The goal of this thesis is to address the function and properties of SLiMs and how they evolved, using bioinformatics methods and evolutionary models. To further examine the role of SLiMs in signal transduction, I show deletion of predicted SLiMs (pSLiMs) have a broad range of quantitative effects on signalling pathway output. Next, to explore what properties are important in substrate recognition, I show that the combination and order of SLiMs can predict target specificity for Clb5, the S phase cyclin. Lastly, using a comparative phylogenetic approach to investigate the evolution of SLiMs, I provide evidence that phosphorylation and docking sites coevolved.
MSc Exit Seminar - Maryna Pilkiw - (Takehara lab)
MSc Exit Seminar
Friday December 9th, 10:10 am - Ramsay Wright Building, Rm. 432
Maryna Pilkiw (Takehara lab)
"Encoding of Physical and Relational Information in the Lateral Entorhinal Cortex"
Abstract
Stimuli are processed more quickly when they are presented within their original context. This phenomenon may depend on neural representations of situational context associated with the history of stimuli encountered in a particular environment. Here we report evidence that cells in the lateral entorhinal cortex (LEC) stably represent the current situation, regardless of moment-to-moment changes in the environment. Ensemble activity in the LEC drastically differentiated six blocks of Pavlovian conditioning, where each block differed in conditioning environment, conditioned stimulus, or the association between a conditioned and unconditioned stimulus. Despite high selectivity for stimulus features, firing rates of most cells were relatively stable throughout the entire conditioning block and marginally changed at stimulus onset. With learning, selectivity for the stimulus relationship improved, while selectivity for other features did not. The stable LEC ensemble code for the current situation may provide the basis for the formation and retrieval of accurate, context-rich memories.
Ramsay Wright is a wheelchair accessible building.
MSc Exit Seminar - Nariman Hossein-Javaheri (Buck Lab)
MSc Exit Seminar
Wednesday September 28th, 12:30 pm - Ramsay Wright Building, Rm. 432
Nariman Hossein-Javaheri (Buck lab)
"Goldfish Pyramidal and Stellate Neurons Respond Differently to Anoxia"
Abstract
With oxygen deprivation the mammalian brain undergoes excito-toxic cell death but this does not occur in the anoxia tolerant goldfish. Since GABA is the major inhibitory neurotransmitter in the brain, I investigated its potential role in preventing hyper-excitability in goldfish telencephalon neurons. Utilizing patch-clamp technique, the electrical activities of both excitatory (pyramidal) and inhibitory (stellate) neurons were recorded. With anoxia, membrane potential depolarized in both cell types. While pyramidal cells remained mostly quiescent, action-potential frequency of the stellate neurons increased. Further, the GABAA receptor reversal potential (EGABA) was depolarizing in both cell types. Inhibition of GABAA receptors reversed the anoxic response, while GABAB receptor inhibition did not induce a response. Co-antagonism of both GABAA/B receptors generated seizure-like neuronal activity. I conclude that GABA is vital for the anoxic survival of the goldfish and that the increased stellate neuron activity likely results in inhibition of pyramidal neuron activity with anoxia.
Ramsay Wright is a wheelchair accessible building.
MSc Exit Seminar - Bardia Nouriziabari (Takehara lab)
MSc Exit Seminar
Thursday September 22nd, 2:10 pm – Earth Sciences Centre, Rm. 3043
Bardia Nouriziabari (Takehara lab)
" ERP-based detection of brain pathology in rat models for preclinical Alzheimer’s disease"
Abstract
Early pathological features of Alzheimer’s disease (AD) include the accumulation of hyperphosphorylated tau protein (HP-tau) in the entorhinal cortex and progressive loss of basal forebrain (BF) cholinergic neurons. These pathologies are known to remain asymptomatic for many years before AD is clinically diagnosed; however, they may induce aberrant brain processing which can be captured as an abnormality in event-related potentials (ERPs). Here, we examined cortical ERPs while a differential associative learning paradigm was applied to adult male rats with entorhinal HP-tau, pharmacological blockade of muscarinic acetylcholine receptors, or both conditions. Despite no impairment in differential associative and reversal learning, each pathological feature induced distinct abnormality in cortical ERPs to an extent that was sufficient for machine classifiers to accurately detect a specific type of pathology based on these ERP features. These results highlight a potential use of ERPs during differential associative learning as a biomarker for asymptomatic AD pathology.