Bulletin of the American Physical Society
APS March Meeting 2016
Volume 61, Number 2
Monday–Friday, March 14–18, 2016; Baltimore, Maryland
Session E55: Delbruck Prize SessionInvited
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Sponsoring Units: DBIO Chair: Steven D. Schwartz, University of Arizona Room: Hilton Baltimore Holiday Ballroom 6 |
Tuesday, March 15, 2016 8:00AM - 8:36AM |
E55.00001: Precision Measurement in Biology Invited Speaker: Stephen Quake Is biology a quantitative science like physics? I will discuss the role of precision measurement in both physics and biology, and argue that in fact both fields can be tied together by the use and consequences of precision measurement. The elementary quanta of biology are twofold: the macromolecule and the cell. Cells are the fundamental unit of life, and macromolecules are the fundamental elements of the cell. I will describe how precision measurements have been used to explore the basic properties of these quanta, and more generally how the quest for higher precision almost inevitably leads to the development of new technologies, which in turn catalyze further scientific discovery. In the 21st century, there are no remaining experimental barriers to biology becoming a truly quantitative and mathematical science. [Preview Abstract] |
Tuesday, March 15, 2016 8:36AM - 9:12AM |
E55.00002: Dynamics of DNA in vitro and in vivo Invited Speaker: Jens-christian Meiners While the structure of DNA has reached iconic status, its dynamics are equally important for its biological function. The thermal fluctuations of DNA gives rise to fundamental properties, such as its entropic elasticity, and enable many biological functions like the formation of regulatory DNA-protein complexes. More recently, evidence is emerging that active, ATP-hydrolysis driven processes also contribute to the motion of DNA in vivo. These active processes can enhance the efficiency of self-assembly processes involving DNA quite substantially. In a living cell, on the other hand, the motion of the DNA is severely constrained by numerous topological barriers, like supercoiling and protein binding, which in turn can locally enhance, but globally restrict the formation of regulatory DNA-protein complexes. In my talk I will review the dynamics of DNA and the interplay between thermal fluctuations, active processes, and topological constraints in the context of in-vitro experiments with optical tweezers, and in-vivo studies of the bacterial chromosome using fluorescence techniques, and interpret the results in the framework of statistical mechanics and polymer physics. [Preview Abstract] |
Tuesday, March 15, 2016 9:12AM - 9:48AM |
E55.00003: Dissecting human cerebral organoids and fetal neocortex using single-cell RNAseq. Invited Speaker: Barbara Treutlein Cerebral organoids -- three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells -- have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. [Preview Abstract] |
Tuesday, March 15, 2016 9:48AM - 10:24AM |
E55.00004: Monitoring of organ transplants through genomic analyses of circulating cell-free DNA. Invited Speaker: iwijn De Vlaminck Solid-organ transplantation is the preferred treatment for patients with end-stage organ diseases, but complications due to infection and acute rejection undermine its long-term benefits. While clinicians strive to carefully monitor transplant patients, diagnostic options are currently limited. My colleagues and I in the lab of Stephen Quake have found that a combination of next-generation sequencing with a phenomenon called circulating cell-free DNA enables non-invasive diagnosis of both infection and rejection in transplantation. A substantial amount of small fragments of cell-free DNA circulate in blood that are the debris of dead cells. We discovered that donor specific DNA is released in circulation during injury to the transplant organ and we show that the proportion of donor DNA in plasma is predictive of acute rejection in heart and lung transplantation. We profiled viral and bacterial DNA sequences in plasma of transplant patients and discovered that the relative representation of different viruses and bacteria is informative of immunosuppression. This discovery suggested a novel biological measure of a person's immune strength, a finding that we have more recently confirmed via B-cell repertoire sequencing. Lastly, our studies highlight applications of shotgun sequencing of cell-free DNA in the broad, hypothesis free diagnosis of infection. [Preview Abstract] |
Tuesday, March 15, 2016 10:24AM - 11:00AM |
E55.00005: Accurate and High-Coverage Immune Repertoire Sequencing Reveals Characteristics of Antibody Repertoire Diversification in Young Children with Malaria Invited Speaker: Ning Jiang Accurately measuring the immune repertoire sequence composition, diversity, and abundance is important in studying repertoire response in infections, vaccinations, and cancer immunology. Using molecular identifiers (MIDs) to tag mRNA molecules is an effective method in improving the accuracy of immune repertoire sequencing (IR-seq). However, it is still difficult to use IR-seq on small amount of clinical samples to achieve a high coverage of the repertoire diversities. This is especially challenging in studying infections and vaccinations where B cell subpopulations with fewer cells, such as memory B cells or plasmablasts, are often of great interest to study somatic mutation patterns and diversity changes. Here, we describe an approach of IR-seq based on the use of MIDs in combination with a clustering method that can reveal more than 80{\%} of the antibody diversity in a sample and can be applied to as few as 1,000 B cells. We applied this to study the antibody repertoires of young children before and during an acute malaria infection. We discovered unexpectedly high levels of somatic hypermutation (SHM) in infants and revealed characteristics of antibody repertoire development in young children that would have a profound impact on immunization in children. [Preview Abstract] |
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