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Information Center for Mathematical Science

세미나

Information Center for Mathematical Science

세미나

KAIST 화학과 세미나

CRISPR/Cas is a revolutionary gene editing technology with wide-ranging utility. The safe, non-viral delivery of gene editing components would greatly improve future therapeutic utility. We will present and report the development of zwitterionic amino lipids (ZALs) that are uniquely able to deliver long RNAs (Cas9 mRNA and targeted sgRNA) from ZAL nanoparticles (ZNPs) to enable gene editing.1 ZALs were synthesized using high efficiency reactions, including ring-opening and addition reactions, providing access to a library of unique charge unbalanced lipids. Delivery of low sgRNA doses (15 nM) can reduce reporter protein expression by >90% in cells. In contrast to transient therapies (e.g. RNAi-mediated mRNA degradation),2-5 we show that ZNP delivery of sgRNA results in permanent DNA modification, where the 95% decrease in protein expression is sustained indefinitely even after multiple rounds of cellular division. ZNP delivery of mRNA results in high protein expression at low doses in vitro (<600 pM) and in vivo (1 mg/kg) in liver, lung and spleen tissue. In mice, intravenous co-delivery of Cas9 mRNA and sgLoxP (4:1 wt ratio; 5 mg/kg total RNA) induced expression of floxed tdTomato in the liver, kidneys, and lungs of genetically engineered mice. Correction of a mutation causing Duchenne muscular dystrophy (DMD) via an exon skipping approach will be highlighted as a functional application of CRISPR/Cas in muscle. We will report the development of the first non-viral delivery system for in vitro and in vivo co-delivery of Cas9 mRNA and targeted sgRNA. The effectiveness of ZNPs for delivery of long RNAs provides a chemical guide for the rational design of future carriers. Such insights have recently allowed reengineering of dendrimer-based lipid nanoparticles3 for mRNA replacement therapy. Moreover, this development of gene editing using synthetic nanoparticles is a promising step towards improving the safety, efficacy, and utility of CRISPR/Cas.1

KAIST 화학과 세미나

Natural organisms such as photosynthetic bacteria, algae, and plants employ complex molecular machinery to convert solar energy into biochemical fuel. An important common feature shared by most of these photosynthetic organisms is that they capture photons in the form of excitons typically delocalized over a few to tens of pigment molecules embedded in protein environments of light harvesting complexes (LHCs). Delocalized excitons created in such LHCs remain well protected despite being swayed by environmental fluctuations, and are delivered successfully to their destinations over hundred nanometer length scale distances in about hundred picosecond time scales. Decades of experimental and theoretical investigation have produced a large body of information offering insights into major structural, energetic, and dynamical features contributing to LHCs’ extraordinary capability to harness photons using delocalized excitons. The objective of this seminar will be (1) to provide a comprehensive account of major theoretical, computational, and spectroscopic advances that have contributed to this body of knowledge, and (2) to clarify the issues concerning the role of delocalized excitons in achieving efficient energy transport mechanisms. The focus will be on three representative systems, Fenna-Matthews-Olson complex of green sulfur bacteria, light harvesting 2 complex of purple bacteria, and phycobiliproteins of cryptophyte algae. Although we will see more in-depth and detailed description of theoretical and computational aspects, major experimental results and their implications are also assessed in the context of achieving excellent light harvesting functionality. Future theoretical and experimental challenges to be addressed in gaining better understanding and utilization of delocalized excitons will also be discussed.

KAIST 화학과 세미나

With its high carbon and hydrogen content, lignocellulosic biomass presents an interesting alternative to petroleum as a nearly carbon-neutral precursor to upgraded liquid fuels. Catalytic fast pyrolysis (CFP) is one of the most promising processes to produce renewable transportation fuels and chemicals from biomass. The widely used zeolite catalysts in CFP of biomass are preferred due to their low cost, low toxicity and high effectiveness at deoxygenating pyrolysis products. Dehydration reactions represent an imporant class of chemical reactions occuring during CFP. Specifically, alcohol dehydration serves as an important, but simple, model reaction. Recent experimental work has shown that the addition of various metals that do not incorporate into zeolite frameworks (“extra-framework metals”) can boost catalytic rates, a phenomenon generally attributed to Lewis acidity conferred by the extra-framework (EF) metal. Recent computational work has also demonstrated the enhancement of Brønsted acidity by nearby EF metal actives species (e.g. Liu et al. ACS Catalysis 2015). Here, we directly compare alcohol dehydration mechanisms with EF gallium species within a “bare” Brønsted acid (no EF metal), “enhanced” Brønsted acid (with EF metal), and Lewis acid contexts. We also present results on preferred binding locations for the various EF gallium species that may be present experimentally with ZSM-5. Experiments were conducted in GCMS/FID system to measure dehydration products from different alcohols. The impact of EF metal on alcohol dehydration yield, reaction rates and catalyst coking will be reported. Other key reactions including dehydrogenation in gasfication process will be also discussed. Diffusion of pyrolysis vapors and their upgraded products in zeolites during CFP is an essential phenomenon, which can influence product separation and selectivity as well as coke formation. Deeper understanding of the effects of zeolite pore size and topology on diffusivity could aid in designing novel zeolites to enhance product separation and selectivity. However, experimental measurements on diffusivity in zeolites are usually difficult, since many pyrolysis vapors will react with activated zeolites at the pyrolysis relevant temperatures. As an alternative approach, molecular dynamics (MD) simulation is a powerful method for addressing this challenge. In this work, we have conducted MD simulations to investigate the diffusivities of several important biofuel model compounds in H-ZSM-5 (Bu et al. J. Phys. Chem. C 2017). Our results demonstrate that in order to develop a correlation to relate a molecular descriptor to diffusivity within zeolites, both the molecular critical size and the molecular weight need to be considered. Furthermore, we have investigated the diffusivity in mesoporous H-ZSM-5 nanosheets, which can be shown to increase access of bulky molecules to active sites and decrease coking. The effect of pore size of mesoporous H-ZSM-5 nanosheets on the diffusivity of coke precursor molecules, such as benzene, naphthalene, and anthracene will be discussed

KAIST 화학과 세미나

Among several reported hexaphyrrin analogues, the hexaphyrin(1.0.1.0.1.0) derivatives, so called rosarins are non-planar, 4nπ (24pi), weakly anti-aromatic macrocycles. Due to their inherent conformational flexibility, the macrocycles exist in many different conformers. Annulation of the β,β′-position of the rosarin by two-carbon bridge, however, makes the macrocycles be planar and strongly anti-aromatic. In addition, the syntheses of peripherally substituted rosarins were hurdled due to the limited accessibility of the key building blocks. Recently, we have developed a synthetic protocol of the new building blocks and successfully utilize those building blocks to the synthesis of the peripherally substituted naphthorosarins. The new compounds displayed unusual redox behavior as well as unusual spectroscopic properties. The degree of the anti-aromaticity varies depending on the substituents. The new planar 24π-antiaromatic systems become stable one-electron reduced species (4n+1)π, (25π) in the presence of various acids (HCl, HBr, TFA and MSA). While, treatment of rosarin with HI yields a corresponding two electron reduced, 26π- aromatic system. On the other hand, simply triprotonated tricationic species was formed upon treatment with perchloric acid. Also, the time-dependent absorption spectral changes indicates that the peripheral substituents affect the redox potentials and anti-aromaticity. Rate of the single electron reduction is faster when fluoride is substituted on the periphery. Detailed studies of the synthesized naphthorosarins including structural property and redox chemistry will be presented in conjunction with a model system for Proton coupled electron transfer (PCET). While extensively studied in a variety of natural systems and a number of discrete metal complexes, PCET mechanisms are less well established in the case of purely organic compounds.

KAIST 화학과 세미나

Traditional methods of making polymer nanostructures with controlled and well-defined morphological features relied largely on post-polymerization self-assembly processes involving gradual change in solvent environment under highly dilute conditions. While such studies were vital in laying out the theoretical and experimental underpinnings of the self-assembly behavior of polymers, application-oriented, scalable production of nanostructures were difficult. Recently, polymer synthesis under heterogeneous conditions have been developed and refined, allowing for the preparation of nanostructures directly from the polymerization reactions. A crucial synthetic element in this approach is the functional moiety that provides the solubility characteristics required to drive nanostructure formation. We have recently identified and utilized two distinct classes of molecules – polysulfide-bearing compounds and para-cyclophane dienes – which are soluble in their monomeric forms but polymerize to give insoluble products. These compounds have been utilized in the direct synthesis of various polymer nanostructures during synthesis. The obtained nanostructures were studied for their potential in applications such as sensing nitroaromatic compounds and heavy metal scavenging in aqueous environments.

KAIST 화학과 세미나

So far, most reported π-conjugated systems in neutral state have a closed-shell ground state. However, recent research disclosed that certain type of π-systems could have an open-shell singlet diradical and even polyradical ground state. In this lecture, I will discuss three types of open-shell polycyclic hydrocarbons developed in our group: (a) zethrenes [1], (b) extended p-quinodimethanes [2], (c) linear and macrocyclic polyradicaloids [3], and 3D cage-like diradiclaoids [4]. The discussion will mainly include their challenging synthesis, their characterizations of the ground-state structures, and their unique optical, electronic and magnetic properties.[5] These fundamental studies now allow us to do rational design of stable open-shell singlet molecules with tunable physical properties and exploit their applications in molecular electronics, spintronics and photonics.[6]

KAIST 화학과 세미나

Synthesis and operation of a nano-demension 24 × 24 × 15 Å3 “left and right ball-joint-type host-guest system” via one π∙∙∙π interaction and three NH∙∙∙O=C hydrogen-bonds along with the combined helicity are described. The system consists of unprecedented conglomerate aggregates of two distinct helical metallacyclophanes, chiral isomer (P)-[Pd3X6(L1)2]@(M)-[Pd3X6(L1)(L2)] and its enantiomer (M)-[Pd3X6(L1)2]@(P)- [Pd3X6(L1)(L2)] are described. Successive reactions afford desirable four-layered metallacyclophanes via tailor-made procedure. Synthesis and operation of a nano-demension size multilayered metallacyclophane system via one π∙∙∙π interaction along with the combined helicity are described. A synthetic strategy of generation of new molecular species utilizing a provision of nature has been reported: nano-dimensional (23(2) × 21(1) × 16(1) Å3) hetero four-layered trimetalla-cyclophanes via the proof-of-concept experiments that utilize a suitable combination of π∙∙∙π interactions between the central aromatic rings, tailor-made short/long spacer tridentate donors, and the combined helicity are constructed. The unprecedented four-layered metallacyclophane system’s behavior offers a landmark in the development of new molecular system.

KAIST 화학과 세미나

The organic electronics is a rapidly emerging area of research with great potential, and encompasses a wide range of material, device and process technologies. In this presentation, a recent progress and the status of organic electronics at Samsung will be presented.

KAIST 화학과 세미나

Two-dimensional nanomaterials such as transition metal dichalcogenides (TMD) and graphene have gained much attention in recent years due to their fascinating physical and chemical properties. To fully exploit these properties in fundamental studies and real applications, it is required to obtain a specimen that has desired geometry (and size) and is placed on a desired substrate. Preparation of such a specimen, or “controlled growth,” is often achieved by vapor-phase growth, namely chemical vapor deposition (CVD), followed by an etching process or a transfer process. In this talk, I present a novel way to achieve controlled growth of two-dimensional nanomaterials using surface alloy as a reaction intermediate. The properties of the product match with previously reports, and the formation of surface alloy as an intermediate is confirmed by spectroscopic and structural analysis.

KAIST 화학과 세미나

The core of regenerative medicine is cell survival rate, precision and biomaterials. ROKIT Biotechnology Printer, INVIVO provides the convergence of technology, which required by regenerative medicine, to develop medical innovation that is already applicable in current clinical settings. This presentation will introduce the present and future of therapeutic methods with the use of 3D bioprinter: in plastic surgery through dermal regeneration, in orthopedic surgery through cartilage regeneration, in ophthalmology for treatment of blindness through retinal cell regeneration, and cardiology surgery for treatment of myocardial infarction through myocardial cell regeneration. In addition, the cell-based technology enables mass production and is able to become a bio-ink, which is made from human-derived decellularized extracellular matrix, providing an environment in which stem cells or cells can best differentiate into desired tissues. Lastly, this presentation will talk about possibilities in the viewpoint of 3D bioprinting; though it is a convergence technology, regenerative medicine should be applied to the field of biomedicine.

KAIST 화학과 세미나

In this talk, I will present advances in computational methods to bridge the gap between computational and experimental methods to study the mechanisms of biomolecules. A brief introduction of the current stages of molecular dynamics and free energy calculations will be given. Afterwards, recent advances on molecular dynamics to overcome the limitations of current simulations will be presented based on three topics. First, I will present a new computational approach, Action-CSA, to find multiple reaction pathways with fixed initial and final states through global optimization of the Onsager-Machlup action using the conformational space annealing method1 . This approach successfully finds all possible pathways of small systems without initial guesses on pathways. Pathway space is efficiently searched by crossover and mutation operations of a set of pathways and preserving the diversity of the set. The search efficiency of the approach is assessed by finding pathways for the conformational changes of alanine dipeptide and hexane. The benchmarks demonstrate that the rank order and the transition time distribution of multiple pathways identified by the new approach are in good agreement with those of long Langevin dynamics simulations. We also show that the lowest action folding pathways of the mini-protein FSD-1 identified by the new approach is consistent with previous molecular dynamics simulations and experiments. Second, I will present constant-pH molecular dynamics methods, which simulate spontaneous changes of protonation states of titratable residues2–4 . The new methods yield the canonical ensemble of multiple protonation states. I will show how these methods are used to perform constant-pH free energy calculations. Third, a new hybrid protein model based on the combination of the physics-based model and the Go-model will be presented5 . This method effectively samples the large-scale conformational changes of adenylate kinase between its open and closed states. The simulation results are showing a good agreement with the backbone fluctuation data obtained with NMR experiments. In summary, these methods will extend the timescale and chemical accuracy of molecular dynamics and free energy calculation methods, which will help to interpret experimental data using theoretical methods.

2018 KAIST Physics Seminar

2018 KAIST Physics Seminar

POSTECH 세미나

한국고등과학원 세미나

These lectures will describe how to think of TFT (or equivalently higher categories) as some kind of (slightly) noncommutative spaces and describe their spectrum, in theory (trying to see the structures physicists find in SUSY gauge theory) and in some examples.

한국고등과학원 세미나

These lectures will describe how to think of TFT (or equivalently higher categories) as some kind of (slightly) noncommutative spaces and describe their spectrum, in theory (trying to see the structures physicists find in SUSY gauge theory) and in some examples.

한국고등과학원 세미나

These lectures will describe how to think of TFT (or equivalently higher categories) as some kind of (slightly) noncommutative spaces and describe their spectrum, in theory (trying to see the structures physicists find in SUSY gauge theory) and in some examples.

POSTECH IBS-CGP Seminar

POSTECH 세미나

Analyses of molecular phenotypes, such as gene expression, transcription factor binding, chromatin accessibility, and translation, is an important part of understanding the molecular basis of gene regulation and eventually organismal-level phenotypes, such as human disease susceptibility. The development of cheap high-throughput sequencing (HTS) technologies with experiment protocols has increased the use of HTS data as measurements of the molecular phenotypes (e.g., RNA-seq, ChIP-seq, ATAC-seq, and Ribo-seq). The HTS data provide high-resolution measurements across the whole genome that represent how the molecular phenotypes vary along the genome. We develop multiple statistical methods that better exploit the high-resolution information in the data and apply them to different biological questions in genomics. In this talk, I will briefly introduce two projects: 1) wavelet-based methods for identification of genetic variants associated with chromatin accessibility, and 2) mixture of hidden Markov models for inference of translated coding sequences.

POSTECH IBS-CGP Seminar