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Plenary Speakers

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Hee-Sup Shin
Code / Date
PL-1 / March 28(Mon) 09:20-10:00
Speaker
Hee-Sup Shin
Affiliation
Institute for Basic Science, Korea
Title
Eye Movement Desensitization and Reprocessing, a psychotherapy for fear disorder, involves the thalamus.
Abstract

Psychotherapies guide treatment of mental disorders and improve the clinical outcomes, although it remains largely unknown how the psychotherapeutic treatment works. Eye movement desensitization and reprocessing (EMDR), a well-established psychotherapy for fear disorders, is based on dual stimulation: recalling a traumatic memory together with orienting to sensory alternating bilateral stimulation (ABS), such as auditory, tactile or commonly visual stimuli. The mechanistic connection between the dual stimulation and fear extinction, however, is unknown. Here, we report that extinction training coupled with visual ABS prevented return of auditory tone-conditioned fear in mice, whereas conventional extinction training, repeated exposures to conditioned tone alone, ended up with fear relapse after a week. Optogenetic experiments revealed that the superior colliculus-mediodorsal thalamus (MD) circuit, a pathway for visual spatial attention, is involved in this process. Thus, optogenetic activation of this circuit facilitated fear extinction, effectively replacing the ABS. Furthermore, during the ABS-coupled extinction training, mediodorsal thalamic (MD) neuronal activities, which are also involved in fear extinction, increased and persisted at a higher level, compared to the conventional extinction training. Consistently, mice with impaired MD firing due to an inactivation of phospholipaseC-4 did not respond to the ABS-mediated enhancement of extinction. In addition, by one week after extinction training, the level of inhibitory transmission in the amygdala became normal in the ABS-coupled extinction group, whereas it was depressed in the conventional extinction group, suggesting a role of the depressed amygdala inhibition in fear relapse. These results reveal the potential neural mechanism underlying the therapeutic effect of EMDR psychotherapy, leading to a block of fear relapse.

 

Robert Moritz
Code / Date
PL-2 / March 28(Mon) 16:00-16:40
Speaker
Robert Moritz
Affiliation
Institute for Systems Biology, USA
Title
Democratization of advances in quantitative proteomics: Multi-omic approaches to biomarker discovery
Abstract

Proteomics technology advances have continued to provide unprecedented levels of both protein identification and quantitation across a multitude of organisms. To capitalize on these advances in comprehensive proteome interrogation, new tools, methods and bioinformatic approaches are required to propel these advances to broad and routine usage. The democratization of these resources enables these tools to be routinely used and enable interrogation of biologically meaningful data so that they can be broadly collected, analyzed and shared within the community. A major goal is to disseminate these developments and applications of proteomic technologies that support comprehensive analysis of all proteins, their isoforms, and post-translational or other modifications contained within the human proteome. This cycle of technology development now allows the proteogenomic application and biological interrogation of disease states to advance the study of biological systems in greater depth and speed to provide new translational efforts in biomarker discovery.

 

Jin-Soo Kim
Code / Date
PL-3 / March 29(Tue) 09:00-09:40
Speaker
Jin-Soo Kim   CV
Affiliation
Institute for Basic Science/Seoul National University, Korea
Title
CRISPR RNA-guided Genome Editing in Human Stem Cells, Animals, and Plants
Abstract

Genome editing that allows targeted mutagenesis in higher eukaryotic cells and organisms is broadly useful in biology, biotechnology, and medicine. We have developed ZFNs, TALENs, and Cas9 RNA-guided endonucleases (RGENs), derived from the type II CRISPR-Cas prokaryotic adaptive immune system, to modify chromosomal DNA in a targeted manner. In particular, we used purified Cas9 protein and in vitro transcribed guide RNAs rather than plasmids encoding these components to correct large chromosomal inversions in the blood coagulation factor VIII gene that cause hemophilia A in patient-derived induced pluripotent stem cells (iPSCs) and to modify diverse genes in large animals and plants. The resulting animals and plants contained small insertions or deletions (indels) at target sites, which are indistinguishable from naturally-occurring variations, possibly bypassing regulatory requirements associated with use of recombinant DNA.
Despite broad interest in RNA-guided genome editing, RGENs are limited by off-target mutations. We developed Cas9 nuclease-digested whole genome (digenome) sequencing (Digenome-seq) to profile genome-wide specificities of Cas9 nucleases in an unbiased manner. Digenome-seq captured nuclease cleavage sites at single nucleotide resolution and identified off-target sites at which indels were induced with frequencies below 0.1%. We also showed that these off-target effects could be avoided by using modified guide RNAs that contain two extra guanine nucleotides at the 5’ end. Digenome-seq is a robust, sensitive, unbiased, and cost-effective method for profiling genome-wide off-target effects of programmable nucleases including Cas9.

 

Kong-Joo Lee
Code / Date
PL-4 / March 29(Tue) 16:00-16:40
Speaker
Kong-Joo Lee   CV
Affiliation
Ewha Womans University, Korea
Title
Proteomics from Target Discovery to Drug Discovery
Career
1986.03-1987.08
Post-doctoral fellow
Biol, Stanford Medical School, USA

1989.03-1994.02
Senior Research Scientist
Division of Chemical Analysis, Korea Research Institute of Standards and Science (KRISS)

1994.03-present
Associate Professor, Professor
College of Pharmacy, Ewha Womans University
Abstract

Recent cutting edge proteomic technologies have been employed for understanding the biological processes using systemic analysis for last 15 years. We will present the proteomic approaches using tandem mass spectrometry developed for identifying the comprehensive and novel protein modifications. Post-translational modifications are key factors to regulate the proteins functions and structures. Employing novel strategy of proteomics, we examined protein expression and post-translational modifications of target proteins in various metastasis and angiogenesis signaling. Based on these methodologies, we identified the disease target proteins, their molecular mechanism in cancer metastasis and their target validation. Furthermore, the chemical modulators of these target proteins were screened and the understandings of molecular action of target proteins and the mode of action of drug candidates are possible employing proteomic tools. We describe a new strategy to identify the target proteins in various diseases, and structural and functional changes of target proteins in response to external stimuli and chemicals. We employed hydrogen/deuterium exchange mass spectrometry (HDX-MS) to identify the binding site and structural changes of target protein by chemical compounds. These cutting edge tools broaden the understanding the point of action of chemical compounds, and make possible to explain the action of newly developed drug candidates. [Supported by the Global Research Lab Program (No. 2012K1A1A2045441) of NRF]