Bulletin of the American Physical Society
APS March Meeting 2019
Volume 64, Number 2
Monday–Friday, March 4–8, 2019; Boston, Massachusetts
Session A64: Physics in Synthetic BiologyFocus Session
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Sponsoring Units: DBIO Chair: Gabor Balazsi, State Univ of NY - Stony Brook Room: BCEC 259B |
Monday, March 4, 2019 8:00AM - 8:36AM |
A64.00001: Synthetic Biology: Physical Biology by Design Invited Speaker: James Collins Synthetic biology is bringing together physicists and biologists to model, design and construct biological circuits out of proteins, genes and other bits of DNA, and to use these circuits to rewire and reprogram organisms. These re-engineered organisms are going to change our lives in the coming years, leading to cheaper drugs, rapid diagnostic tests, and synthetic probiotics to treat infections and a range of complex diseases. In this talk, we highlight recent efforts to create synthetic gene networks and programmable cells, and discuss a variety of synthetic biology applications in biophysics, biotechnology and biomedicine. |
Monday, March 4, 2019 8:36AM - 9:12AM |
A64.00002: Designing Physical Synthetic Biology Invited Speaker: Chris Voigt TBD |
Monday, March 4, 2019 9:12AM - 9:24AM |
A64.00003: Multiscale Effects of Temperature on Synthetic Gene Circuits Daniel Charlebois, Kevin Hauser, Sylvia Marshall, Gabor Balazsi Synthetic gene circuits are rationally designed gene networks that perform predefined functions, and have promising applications in many areas including agriculture, bioenergy, and biomedicine. However, synthetic gene circuits are built and characterized in laboratory settings where extracellular variables, such as temperature, are maintained at optimal levels. To study how nonoptimal temperatures (as in real-world conditions) affect the function of synthetic gene networks, we combined multiscale computational modeling with experiments in genetically engineered budding yeast Saccharomyces cerevisiae. We discovered that nonoptimal temperatures induce a cell fate choice between stress resistant and growth arrested phenotypes. Overall, we found that four key effects are required to fully predict the effect of nonoptimal temperatures across different biological scales: 1) cell fate choice between arrest and resistance, 2) slower growth rates, 3) Arrhenius dependence of reaction rates, and 4) changes in protein structure. These findings advance our understanding of how temperature affects living systems and enable more robust genetic engineering for real-world applications. |
Monday, March 4, 2019 9:24AM - 9:36AM |
A64.00004: On the noise of gene expression in membrane-bound picolitre biochemical reactors Ziane IZRI, Ryota Sakamoto, Vincent Noireaux, Yusuke T. Maeda A clonal population, sharing exactly the same genetic information, eventually displays variability in its observed metabolic properties, such as protein concentrations [1]. |
Monday, March 4, 2019 9:36AM - 9:48AM |
A64.00005: CRISPRgates: Programmable and Orthogonal Gene Circuit Elements David Specht, Guillaume Lambert While CRISPR may be better-known as a gene editing tool, it can also be used as a tool for selective repression of genes using a catalytically-dead CRISPR nuclease. Here, we exploit both the freedom in the CRISPR identification region as well as the freedom in promoter design to create a set of 128 synthetic ‘barcoded’ promoters in E. coli, each of which is keyed to a specific CRISPR guide RNA. These synthetic promoters can then be used to drive chosen genes in modular fashion. We take a multiplexed approach using ‘randomized’ promoter barcodes to demonstrate orthogonality of the ‘CRISPRgates’ on a large scale. This method is immediately transferrable to many different CRISPR nucleases, including Cas9, Cas12a, Cas13a, and CasX, and we use it to study and contrast the behavior of these different systems and probe their properties, including the crRNA structure and PAM site sequence. We then explore how these orthogonal circuit elements can be exploited to create complex genetic circuits. These gates function as transcriptional NOT gates but are Boolean-complete and can in principle be assembled to produce time-dynamic gene circuits. |
Monday, March 4, 2019 9:48AM - 10:00AM |
A64.00006: Development of a new measurement standard for synthetic circuit design Bin Shao, Chris Voigt Large-scale engineering of biological circuits requires reliable measurements of genetic parts and a deep understanding of interactions between synthetic circuits and the host cell. However, the widespread adoption of non-physical units of measurement makes it difficult to parameterize synthetic parts and cellular context, which hinders the efforts to model multi-component synthetic circuits in a predictable way. Here we present a new measurement standard in which DNA- and RNA- binding proteins fused with spectrally well-separated fluorescent proteins are used to visualize plasmid and mRNA simultaneously. By combining quantitative fluorescence microscopy with a customized image processing pipeline, we are able to quantify promoter copy number, RNA production and protein abundance at the single cell level. This allows us to determine biophysical parameters of genetic devices, such as the RNA polymerase flux of a standard promoter. We also show that the new measurement standard can be further applied to investigate the transcriptional power of bacteria cells. |
Monday, March 4, 2019 10:00AM - 10:12AM |
A64.00007: Quantification of randomized programmable CRISPR-based toggle switches in Escherichia coli Yasu Xu, Guillaume Lambert Recent developments and advances in CRISPR-Cas (Clustered regularly interspaced short palindromic repeats and CIRSPR-associated proteins) systems have ushered a new generation of powerful genetic engineering tools in synthetic biology. In particular, a catalytically ‘dead’ version of CRISPR-Cas proteins that lack nuclease activity can essentially function as a logic NOR gate by selectively binding to a promoter sequence and preventing initiation of transcription by RNA polymerase. In this work, we create programmable and compact genetic toggle switches using pairs of mutually repressible orthogonal CRISPR-based NOR gates and measure the strength of these toggle switches in parallel using a next-generation sequencing method called “Cross-Seq”. Pairs of tandem positioned CRISPR toggle switch with randomized target barcode are inserted into plasmid and transformed into E. coli cells. Each toggle switch output controls a selectable or counter-selectable marker and, by the positively and negatively selecting for bacteria survival, we are able to measure the output of co-repressing NOR gates in all possible combinations and simultaneously quantify the relative strength and stability of dozens of toggle switches in parallel. |
Monday, March 4, 2019 10:12AM - 10:24AM |
A64.00008: Out-of-equilibrium microcompartments for the bottom-up integration of metabolic functions in population of artificial microsystems Thomas Beneyton, Dorothee Krafft, Claudia Bednarz, Christin Kleinberg, Christian Woelfer, Ivan Ivanov, Tanja Vidkovic-Koch, Kai Sundmacher, Jean-Christophe Baret Self-sustained metabolic pathways in microcompartments are the corner-stone for living systems. From a technological viewpoint, such pathways are a mandatory prerequisite for the reliable design of artificial cells functioning out-of-equilibrium. We develop microfluidic platforms for the miniaturization and analysis of metabolic pathways in man-made compartments formed of water-in-oil droplets [1]. In a modular approach, we integrate a nicotinamide adenine dinucleotide (NAD)-dependent enzymatic reaction and a NAD-regeneration module as a minimal metabolism. We show that the functionalized microcompartments sustain a metabolically active state until the substrate is fully consumed. Reversibly, the external addition of the substrate reboots the metabolic activity of the microcompartments back to an active state. We therefore control the metabolic state of thousands of independent monodisperse microcompartments, a step of relevance for the construction of large populations of metabolically active artificial cells. The next challenges would be the coupling of our chemical functionalization with mechanical functions to design active micro-systems with life-like properties. |
Monday, March 4, 2019 10:24AM - 10:36AM |
A64.00009: Synthetic Gene Circuits Controlling Precise Biological Pattern Formation in Multicellular-Mammalian Systems Tyler Guinn, Gabor Balazsi Small molecules offer a diverse range of tools for probing fundamental principles of biological organization and hierarchy in biological physics. Yet, despite their strengths for controlling temporal biological functions, they are limited in exploring questions relevant to biological pattern formation. To address this need for studying spatiotemporal phenotypes in multicellular systems, we have created a toolbox of multiple light-inducible gene circuits that can tune gene expression and control levels of transcriptional noise at the single cell level. We accomplish this by engineering the tetracycline gene-expression system to convert light stimuli information into cellular response proteins in a spatiotemporal context with single-cell resolution. These circuits are built using the light responsive proteins LOV2 & VVD, a small peptide synthesized by the cell, and a light-inducible degradation tag. The resulting tools provide a platform for robust gene expression control in a spatiotemporal fashion, allowing easy exchange for genes of interest and probing physical biology questions in the context of cell-to-cell communication. |
Monday, March 4, 2019 10:36AM - 10:48AM |
A64.00010: Drop chemostats on a chip Elad Stolovicki, Lloyd Ung, roy ziblat, David A Weitz The adaptation process of biological system to novel challenge has a lot of variability. To investigate the spectrum of possible adaptation trajectories requires large ensemble of identical twin population. To address this challenge, we are developing a drop-based microfluidic device with hundreds of chemostats on a single chip. The chemostat is a continuous-culture apparatus that enables growth of cells in a well-controlled environment. The controlled conditions of the chemostat enable the measurement of population response to specific factor by varying only one environmental factor at a time. In the drop microfluidic approach, the chemostat vessel is ~1µL media drop surrounded by inert oil. Every population in every drop is an independent chemostat population. Each chemostat droplet is continuously diluted with fresh media. The flow of the chemostat drop insure the mixing of nutrient and suspension of the cells. The surrounding oil reduce the fouling of cells to the channel walls. The measurements can be done on the whole chemostat drop or only on the subtracted fraction. The subtracted fraction from the chemostat can be used to monitor the cells and environment in the drop using variety of distractive assays without interfering the chemostat experiment. |
Monday, March 4, 2019 10:48AM - 11:00AM |
A64.00011: Nanoelectronic lab-on-a-chip sensors to detect and monitor DNA hybridization Delphine Bouilly, Claudia Marcela Bazan, Madline Sauvage, Mohamed OUQAMRA, Amira Bencherif Nanoelectronic circuits are emerging as a promising technology for lab-on-a-chip, molecular-scale biosensors. In this presentation, I will present the design of such sensors using functionalized nanocarbon materials and their principle of operation to detect and monitor the hybridization of DNA sequences. Carbon nanotubes or graphene ribbons are immersed in a microfluidics platform and functionalized with single-stranded DNA. Hybridization of the tethered DNA with its complementary sequence induces a specific change in the electrical conductance of the devices. First, I will present recent experiments based on this design to detect specific DNA sequences. Second, I will describe the miniaturization of this approach to the single-molecule scale, and its application to monitor DNA hybridization dynamics with single-molecule resolution. Finally, I will discuss applications of this emerging technique for lab-on-a-chip biomedical technology. |
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