Integrated Calendar

The talk will present new expected and unexpected results from the Dark Energy Survey beyond cosmological studies:
e.g. solar system objects, Milky Way companions, galaxy clusters, and high-redshift objects.

: Neuronal plasticity is a unique property that describes the ability of the system to undergo long-lasting changes, typically as a result of experience. This paradigm, initially discovery by Bliss and Lomo and dubbed long term potentiation (LTP), describes a scenario where the post-synaptic responses increase in strength for long durations, following a particular pre-synaptic stimulus. Conversely, LT-Depression, describes the long lasting depression of synaptic responses. Today, these phenomena are commonly used to describe the molecular model for learning and memory. A large body of work has implicated more than a hundred proteins and factors in modulating LTP and LTD, and thereby memory. Unfortunately, there is still a lively debate regarding the true necessity and exact role of each player. The need for new techniques and approaches to further explore synaptic function and dysfunction has never been more pressing, as the number of people developing neurodegenerative diseases rises exponentially to epidemic scales, with the aging population. These diseases are characterized by a strong decline in the number of synapses and in the ability of synapses to undergo plasticity, ultimately resulting in the severe decline of cognitive function- such as learning and memory. To better scrutinize synaptic plasticity and probe the function and role of its initiators (i.e. NMDA receptors and calcium ions), I have developed novel light-gated NMDA receptors and photoactivatable fluorescent Ca2+-probes to monitor synaptic activity with unmet spatio-temporal resolution and reversibility. I use the latter to examine the roles of specific NMDA-receptor subunits in plasticity.

Protein homeostasis in the cell is regulated by two highly conserved pathways, the UPS and the autophagy. So far the link between these pathways was mainly evaluated by blocking the degradation flux through either pathway, thus limiting the ability to accurately assess the cross talk between the two systems. Here we demonstrate that knockdown of the proteasome integral ubiquitin receptors S5a and ADRM1, impairs polyubiquitinated substrate degradation by the 26S proteasome, while avoiding the global deleterious outcomes associated with proteasome inhibitors. We demonstrate that p62-mediated autophagy effectively balances the reduced proteasome capacity. Finally, we provide evidence for the mechanism linking the regulation of p62 expression with proteasome activity. We propose that upon impairment of the proteasomal flux short-lived transcription factors constitute an inherent feedback loop that upregulate p62 dependent autophagy, thereby maintaining cellular proteostasis and prevent the formation of protein aggregates.