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TGIF Spring - Summer 2017


Schedule:



Dates can change, (check this page often!)


Speaker

Mike Hou, Hongli Chen, Shuo Shi, Sanhong Liu, Bei Yang, Intaek Lee

Time

3:00 PM, Friday,  July 21st, 2017

Venue Students' Hall, 3rd Floor, Building 6, No.99 Haike Rd
Title TGIF Meeting--Sharing Session
Sponsor




Past Events:


Speaker

Sergio Durante

Time

4:00 PM, Thursday, July 6th, 2017

Venue Faculty Lounge, 3rd Floor, Building 6, No.99 Haike Rd
Title Music knowledge for the knowledgeable ¨C a one hour conversation

Abstract

The purpose of the presentation is unambitious: to spend ca. 60 pleasant minutes with knowledgeable colleagues listening and examining a few pieces of music from different traditions, both Western and Eastern and point to the problems and prospects of music education at the time of globalization. This involves on one hand re-defining the limits of the ¡®standard repertoire¡¯ and on the other to articulate a more appropriate approach to the so called ¡®music theory¡¯.
Sponsor


Speaker

Erez Lieberman Aiden

Time

3:00 pm, Wednesday, June 14th, 2017

Venue Students' Hall, 3rd Floor, Building 6, No.99 Haike Rd
Title 3D Codes in the Human Genome

Abstract


Stretched out from end-to-end, the human genome ¨C a sequence of 3 billion chemical letters inscribed in a molecule called DNA ¨C is over 2 meters long. Famously, short stretches of DNA fold into a double helix, which wind around histone proteins to form the 10nm fiber. But what about longer pieces? Does the genome¡¯s fold influence function? How does the information contained in such an ultra-dense packing even remain accessible?
In this talk, I describe our work developing ¡®Hi-C¡¯ (Lieberman-Aiden et al., Science, 2009; Aiden, Science, 2011) and ¡®in-situ Hi-C¡¯ (Rao & Huntley et al., Cell, 2014), which use proximity ligation to transform pairs of physically adjacent DNA loci into chimeric DNA sequences. Sequencing a library of such chimeras makes it possible to create genome-wide maps of physical contacts between pairs of loci, revealing features of genome folding in 3D.
Next, I will describe our work using in situ Hi-C to construct haploid and diploid maps of genome folding in many cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and which segregate into six subcompartments. We identify tens of thousands of loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species.
Interestingly, one class of loops typically occurs at domain boundaries, thereby creating ¡°loop domains.¡± The anchors of these loops bind the protein CTCF and the ring-shaped cohesin complex. The CTCF motifs at these loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs ¡°facing¡± one another. Thus, the position and orientation of CTCF sites forms a 3D code in the human genome. Notably, our data is consistent with a model in which loop domains form by extrusion (Sanborn & Rao et al., PNAS, 2015). By modifying CTCF motifs using CRISPR, we can reliably add, move, and delete loops and domains. By degrading cohesin, we can disrupt all loop domains genome-wide, measure the speed at which loops are extruded, and gauge the impact of loop domains on transcription (Rao et al., Biorxiv, 2017).
Finally, I will note that, while many loops form by extrusion, not all loops do so. The CTCF code is but one of many 3D codes in the human genome.
Sponsor



Speaker

Xiaoling Song

Time

3:00 PM, Friday,  June 2nd, 2017

Venue Students' Hall, 3rd Floor, Building 6, No.99 Haike Rd
Title Atomic 3D reconstruction of gold nanoparticles by electron microscopy - When low dose meets high resolution

Abstract


Water-soluble gold nanoparticle (AuNPs) of 1-2 nm in diameter are highly demanded.  Biocompatible application might only work with small water-soluble particles and theoretical and experimental characterization of this size region is probably the most challenging.  Structure determination of AuNPs is necessary for understanding their physical and chemical properties, and only one water-soluble AuNP larger than 1 nm in diameter, an Au102NP, has been solved to atomic resolution.  Au102NP structure was determined by X-ray crystallography, other large AuNPs have been crystallized, but X-ray diffraction has not extended to atomic resolution.  We report the structure determination of an Au68NP at atomic resolution by aberration-corrected transmission electron microscopy (AC-TEM), an approach that could be extended to any type of AuNPs.  The use of image conditions from TEM of biological particles, a low dose strategy, was instrumental to reconstruct the 3D arrangement of individual gold atoms.  Data collection was performed with the use of a minimal electron dose to avoid beam damage. A cluster of 68 gold atoms was observed, and 32 thiols could be accommodated on the surface. The result was supported by comparison of observed infrared absorption spectra with those calculated by density functional theory for Au68(SR)32, as well as by small angle X-ray scattering, mass spectrometry, thermogravimetric analysis, and X-ray photoelectron scattering.

Sponsor


Speaker

Han Cao, Ph.D. &  Michael Y. Xie, Ph.D.

Time

3:00 PM, Friday,  May 26th, 2017

Venue Students' Hall, 3rd Floor, Building 6, No.99 Haike Rd
Title Next-Generation Mapping with NanochannelArray : Application to Clinically Relevant Structural Variation Analysis & Introduction of Jing Medicine Ltd.

Abstract


Next-generation mapping (NGM) using the BioNano Genomics Irys® System offers high-throughput, genome-wide method, based on direct visualization of extremely long, intact DNA molecules. The system allows researchers to interrogate genomic structural variations (SVs) of one kilobase pairs and above. The Irys System uses extremely long range information to span interspersed and long tandem repeats making it suitable for elucidating the structure and copy number of complex regions of the human genome, such as loci with complex pseudogene and paralogous gene families. Because NGM is a de novo process and the analyzed molecules are longer than most genomic repeats, NGM is able to detect a wide range of SVs including insertions of novel sequence, tandem duplications, interspersed duplications, deletions, inversions and translocations. Various subsets of those SVs could potentially be detected by one or more of the following technologies, i.e. whole-exome sequence (WES) or whole-genome sequencing (WGS), long-read sequencing, chromosomal microarray (CMA), karyotyping or fluorescence in situ hybridization (FISH), however none can detect the full array of mutation types that NGM can detect. Additionally, some SVs are likely to be found only by NGM. Because of the high speed, low cost, genome wide nature and comprehensiveness of the SV types detected, NGM is increasingly being applied to the analysis of clinical genomes for the detection of SVs potentially involved in disease pathogenesis. We present several case studies showing the power of NGM to detect translocations and copy number variants in leukemia as well as de novo mutations in patients analyzed in conjunction with their parents in diseases such as Autism, Pontine tegmental cap dysplasia (PTCD), Aicardi and other undiagnosed disease. NGM is a fast and cost effective method for detection of a range of SVs across the entire genome that cannot be detected by any single technology.

Jing medicine is an innovative high-tech biopharmaceuticals enterprises, located in Shanghai Pudong New District. Established in 2017, with 130 million RMB capital fund, the company is committed to the development of therapeutic humanized monoclonal antibody and small molecule drugs. Several research projects currently in the pre-clinical stage owns their rights of intellectual property. A number of projects have formed domestic and international collaboration.  The core R & D and management team members are composed of senior scientists from the United States, with extensive experience in world-class biopharmaceutical companies in research and development and management. The company is a foreign joint venture, investors have strong background in pharmaceutical industry and excellent experience in the bio-pharmaceutical investment field.

Sponsor


Speaker

Xiaoling Song

Time

4:00 PM, Friday,  May 12th, 2017

Venue Students' Hall, 3rd Floor, Building 6, No.99 Haike Rd
Title Overcome drug resistance to targeted therapy in non-small cell lung cancer

Abstract


Lung cancer is a world-wide leading cause of cancer related death. Lung cancer also has a very high incidence rate, and recently this rate is rapidly increasing. The initiation of precision medicine in the world including China provides a great benefit for lung adenocarcinoma patients who have epidermal growth factor receptors (EGFR) mutations or ALK gene rearrangement. Gene-informed personalized medicine has significantly prolonged progression-free survival and improved the life quality of lung cancer patients. However, the existance of tumor relapse and drug resistance results in long term treatment failure, which greatly hindered the small molecule based targeted therapy in lung cancer. Dr. Song use transgenic animal model and cancer cell lines to study the resistance mechanism in lung cancer. Knowledge gained from this study is to help to improve gene-directed therapies and guide more effective strategies to treat mutation-mediated lung adenocarcinomas.
Sponsor


Speaker

Jakob Ulmschneider

Time

3:00 PM, Friday,  April 14th, 2017

Venue Students' Hall, 3rd Floor, Building 6, No.99 Haike Rd
Title How membrane active peptides partition into bilayers and spontaneously assemble into functional membrane proteins

Abstract


Antimicrobial peptides (AMPs) are a key component of the innate immune defense of all forms of life, but the mechanisms driving their antimicrobial activity are only poorly understood. AMPs are known to preferentially bind to microbial membranes and form pores. However, how AMPs selectively target microbial membranes and the relationship between pore-formation and antimicrobial activity remains largely undetermined. This is chiefly due to the lack of atomic detail structural information detailing the mechanisms of membrane binding and channel formation, as well as the pore architecture.
Previous attempts at determining the structures of AMP channels have been thwarted by the transient nature of AMP channels. Here we demonstrate and experimentally validate a new methodology, based on unbiased atomic detail equilibrium molecular dynamics simulations, that allows direct ab initio assembly of functional AMP pores. This approach accurately predicts the insertion mechanisms and native state structures of membrane active peptides at atomic resolution, accurately reproducing experimental ensemble averages and partitioning data synchrotron radiation circular dichroism spectroscopy and in vitro translocon experiments [1-2]. The insertion probability as a function of peptide length follows two-state Boltzmann statistics and reveals atomic-resolution details about the partitioning process. Here we demonstrate the further extension of this methodology to capture the spontaneous assembly of peptides into functional channels in the bilayer.
Sponsor


Speaker

Lan Xu

Time

3:00 PM, Friday,  March 31st, 2017

Venue Students' Hall, 3rd Floor, Building 6, No.99 Haike Rd
Title Protein Structure-Function and Design, Applications in Drug Discovery

Abstract


Nature utilizes proteins to exert various important biological functions.  With advent of new protein engineering techniques, from direct evolution, structure-based and mechanism-based rational approaches to computer-aided directed evolution, enzymes with desired activities, stabilities, enantioselectivity, substrate specificities, product selectivity, and even novel catalytic functions have been developed. As examples, an evolved nitrile hydratase with superb enantioselectivity is incorporated in a chemoenzymatic process to produce epileptic drug levetiracetam.  Engineered key pathway enzymes in a semi-synthetic biosynthetic pathway for production of terpene-based therapeutics enabled an optimal pathway flux.
My research interests: Utilizing integrative structural characterization tools and other biophysical techniques to study the structure-function relationship of immunological important macromolecules, structure-based drug design and protein engineering for protein therapeutics development.
Sponsor


Speaker

Germano Nardini

Time

3:30 PM, Friday,  March 10th, 2017

Venue Students' Hall, 3rd Floor, Building 6, No.99 Haike Rd
Title Gravitational waves: a novel way to probe the universe and its particle content

Abstract


The groundbreaking detection of gravitational waves by the aLIGO collaboration has started a new era. It has not only proven that gravitational waves exist but also that we are able to detect them with an accuracy that allows to detail the features of the sources. Unprecedented knowledge on astrophysics, cosmology and particle physics can be accessed in this way.  In this talk we will provide an overview on the status of this field. We will review the general ideas about the physical processes producing gravitational waves and describe the novel knowledge that we expect to acquire in the forthcoming future. In particular, by considering some illustrative sources, we will explain how we can analyze gravitational wave signals to infer information about black hole configurations, about the first seconds of the universe, and eventually about the fundamental particles that we and our surroundings are made of.
Sponsor



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