107 research outputs found
On the effective action of confining strings
We study the low-energy effective action on confining strings (in the
fundamental representation) in SU(N) gauge theories in D space-time dimensions.
We write this action in terms of the physical transverse fluctuations of the
string. We show that for any D, the four-derivative terms in the effective
action must exactly match the ones in the Nambu-Goto action, generalizing a
result of Luscher and Weisz for D=3. We then analyze the six-derivative terms,
and we show that some of these terms are constrained. For D=3 this uniquely
determines the effective action for closed strings to this order, while for D>3
one term is not uniquely determined by our considerations. This implies that
for D=3 the energy levels of a closed string of length L agree with the
Nambu-Goto result at least up to order 1/L^5. For any D we find that the
partition function of a long string on a torus is unaffected by the free
coefficient, so it is always equal to the Nambu-Goto partition function up to
six-derivative order. For a closed string of length L, this means that for D>3
its energy can, in principle, deviate from the Nambu-Goto result at order
1/L^5, but such deviations must always cancel in the computation of the
partition function. Next, we compute the effective action up to six-derivative
order for the special case of confining strings in weakly-curved holographic
backgrounds, at one-loop order (leading order in the curvature). Our
computation is general, and applies in particular to backgrounds like the
Witten background, the Maldacena-Nunez background, and the Klebanov-Strassler
background. We show that this effective action obeys all of the constraints we
derive, and in fact it precisely agrees with the Nambu-Goto action (the single
allowed deviation does not appear).Comment: 71 pages, 7 figures. v2: added reference, minor corrections. v3:
removed one term from the effective action since it is trivial. The
conclusions on the corrections to energy levels are unchanged, but the claim
that the holographic computation shows a deviation from Nambu-Goto was
modified. v4: added reference
Bottom-up construction of complex biomolecular systems with cell-free synthetic biology
Cell-free systems offer a promising approach to engineer biology since their open nature allows for well-controlled and characterized reaction conditions. In this review, we discuss the history and recent developments in engineering recombinant and crude extract systems, as well as breakthroughs in enabling technologies, that have facilitated increased throughput, compartmentalization, and spatial control of cell-free protein synthesis reactions. Combined with a deeper understanding of the cell-free systems themselves, these advances improve our ability to address a range of scientific questions. By mastering control of the cell-free platform, we will be in a position to construct increasingly complex biomolecular systems, and approach natural biological complexity in a bottom-up manner
Principles of genetic circuit design
Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552
Cell-free synthetic biology for in vitro prototype engineering
Cell-free transcription-translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test-kits for onsite identification of viruses (Zika, Ebola), whilst gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. The next stages of cell-free look set to unlock new microbial hosts that remain slow to engineer and unsuited to rapid iterative design cycles. It is hoped that the development of such systems will provide new tools to aid the transition from cell-free prototype designs to functioning synthetic genetic circuits and engineered natural product pathways in living cells
Microfluidics: reframing biological enquiry
The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science
Brain Organoids—A Bottom-Up Approach for Studying Human Neurodevelopment
Brain organoids have recently emerged as a three-dimensional tissue culture platform to study the principles of neurodevelopment and morphogenesis. Importantly, brain organoids can be derived from human stem cells, and thus offer a model system for early human brain development and human specific disorders. However, there are still major differences between the in vitro systems and in vivo development. This is in part due to the challenge of engineering a suitable culture platform that will support proper development. In this review, we discuss the similarities and differences of human brain organoid systems in comparison to embryonic development. We then describe how organoids are used to model neurodevelopmental diseases. Finally, we describe challenges in organoid systems and how to approach these challenges using complementary bioengineering techniques
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