Integrated Calendar

The complex hierarchy of three-dimensional patterns that characterize the 3D folding of mammalian chromosomes appears as an important element in controlling gene expression. At the megabase scale, chromosomes are partitioned into domains that define two main compartments, corresponding to transcriptionally active and inactive regions, respectively. Each compartment domain is itself composed of distinct domains characterized by increased self-interactions called topological domains (TADs). Recent high-resolution Hi-C approaches revealed a finer-scale organisation of the genome in smaller “contact domains”, often associated with loops linking specific points. At these different scales, the spatial organisation of the genome shows tight correlation with its chromatin structure and its transcriptional activity. However, while steady progress is being made in describing the 3D folding of the genome at increased resolution, the mechanisms that determine this folding, its dynamic properties and the functional implications of these emerging features are still poorly understood.
We use advanced genome tagging and engineering strategies, as well as targeted inactivation of factors involved in chromosomal folding to unravel the elements and mechanisms that drive the folding of large loci in specific yet dynamic conformations and their influence on gene expression. Our recent results show that the complex patterns of vertebrate HiC maps result from the superimposition of two distinct mechanisms: 1) a cohesin-independent mechanism which brings together regions of similar chromatin states 2) a cohesin-dependent folding that associate different small compartments into TADs. Within TADS, we show as well that enhancers are not acting in a homogeneous manner, but that their influence is distributed in complex patterns, partially guided by the underlying structure. I will discuss the different implications of these findings for our views of genome organisation.

Illumination of supercooled microliter water drops on a hydrophobic glass slide with pulsed ns-laser beams induces ice nucleation. The type of the ice nucleation, heterogeneous or homogeneous is determined by the illumination configuration. When analyzing the enhancement of the X-ray diffraction peaks from frozen drops and the first appearance of diffraction peak from the growing nuclei in a liquid drop by X-ray pulse after each laser pulse, a correlation to the polarization state is seen. This points toward the mechanism where the electric field defines preferred direction for water molecules to bind via the interaction between laser-induced dipoles. Furthermore, the latter observations also reveal particle ice attachment during growth. Finally, different illumination configurations yield freezing temperatures that can be higher by about 10 °C than from non-irradiated water drops.

Understanding the functional communication across brain has been a long sought-after goal of neuroscientists. However, due to the widespread and highly interconnected nature of brain circuits, the dynamic relationship between neuronal network elements remains elusive. With the development of optogenetic functional magnetic resonance imaging (ofMRI), it is now possible to observe whole-brain level network activity that results from modulating with millisecond- timescale resolution the activity of genetically, spatially, and topologically defined cell populations. ofMRI uniquely enables mapping global patterns of brain activity that result from the selective and precise control of neuronal populations. Advances in the molecular toolbox of optogenetics, as well as improvements in imaging technology, will bring ofMRI closer to its full potential. In particular, the integration of ultra-fast data acquisition, high SNR, and combinatorial optogenetics will enable powerful systems that can modulate and visualize brain activity in real-time. ofMRI is anticipated to play an important role in the dissection and control of network-level brain circuit function and dysfunction. In this talk, the ofMRI technology will be introduced with advanced approaches to bring it to its full potential, ending with examples of dissecting whole brain circuits associated with neurological diseases utilizing ofMRI.

Short Bio:
Dr. Lee received her Bachelor’s degree from Seoul National University and Masters and Doctoral degree from Stanford University, all in Electrical Engineering. She is a recipient of the 2008 NIH/NIBIB K99/R00 Pathway to Independence Award, 2010 NIH Director’s New Innovator Award, 2010 Okawa Foundation Research Grant Award, 2011 NSF CAREER Award, 2012 Alfred P. Sloan Research Fellowship, 2012 Epilepsy Therapy Project award, 2013 Alzheimer’s Association New Investigator Award, 2014 IEEE EMBS BRAIN young investigator award, and the 2017 NIH/NIMH BRAIN grant award. As an Electrical Engineer by training with Neuroscience research interest, her goal is to analyze, debug, and engineer the brain circuit through innovative technology.

1. Hyun Joo Lee†, Andrew Weitz†, David Bernal-Casas, Ben A. Duffy, Mankin Choy, Alexxai Kravitz, Anatol Kreitzer, Jin Hyung Lee*, Activation of direct and indirect pathway medium spiny neurons drives distinct brain-wide responses, Neuron, 2016;91(2):412-424.

2. Jia Liu†, Ben A. Duffy†, David Bernal-Casas, Zhongnan Fang, Jin Hyung Lee*, Comparison of fMRI analysis methods for heterogeneous BOLD responses in block design studies, Neuroimage, 2017;147:390-408.

3. David Bernal-Casas, Hyun Joo Lee, Andrew Weitz, Jin Hyung Lee*, Studying brain circuit function with dynamic causal modeling for optogenetic fMRI, Neuron, 2017;93:522-532.

Medicine is taking its first steps towards patient-specific care. Nanoparticles have many potential benefits for treating cancer, including the ability to transport complex molecular cargoes including siRNA and protein, as well as targeting to specific cell populations.
The talk will address principles for engineering drug-loaded nanoparticles that can be remotely triggered to release their payload in disease sites. The evolution of such nanoparticles into programmed nano robots, unique particles that have an internal capacity to synthesize protein drugs, and their promise for treating cancer, will be discussed.
Our research is aimed at tailoring treatments to address each person’s individualized needs and unique disease presentation. Specifically, we developed barcoded nanoparticles that target sites of cancer where they perform a programmed therapeutic task. These systems utilize molecular-machines to improve efficacy and reduce side effects.

Reversible modulation of neuronal activity is a powerful approach for isolating the roles of specific neuronal populations in circuit dynamics and behavior. Optogenetics enables such experiments, through excitation and inhibition of defined cells within neural circuits. However, in contrast to optogenetic excitation, for which a limited number of optogenetic tools can serve to all but a few experimental needs, tools used for inhibition of neuronal activity still impose stringent constraints on the experimental paradigm. During the seminar I will present data showing that the optimal approach for optogenetic silencing differs between subcellular neuronal compartments, characterize current tools for axonal inhibition and introduce a set of soma-targeted naturally-occurring anion-conducting channelrhodopsins as the potential next generation of inhibitory optogenetic tools for somatodendritic silencing approaches in neuroscience.