Tom Knight

Ginkgo Bioworks Inc.

Mesoplasma florum, a fast-growing near-minimal organism, is a compelling model to explore rational genome designs. Using sequence and structural homology, the set of metabolic functions its genome encodes was identified, allowing the reconstruction of a metabolic network representing ˜ 30% of its protein-coding genes. Growth medium simplification e...

The near-minimal bacterium Mesoplasma florum is an interesting model for synthetic genomics and systems biology due to its small genome (~800 kb), fast growth rate, and lack of pathogenic potential. However, fundamental aspects of its biology remain largely unexplored. Here, we report a broad yet remarkably detailed characterization of M. florum by...

Synthetic biology relies on the manufacture of large and complex DNA constructs from libraries of genetic parts. Golden Gate and other Type IIS restriction enzyme-dependent DNA assembly methods enable rapid construction of genes and operons through one-pot, multi-fragment assembly, with the ordering of parts determined by the ligation of Watson-Cri...

Modern synthetic biology depends on the manufacture of large DNA constructs from libraries of genes, regulatory elements or other genetic parts. Type IIS-restriction enzyme-dependent DNA assembly methods (e.g., Golden Gate) enable rapid one-pot, ordered, multi-fragment DNA assembly, facilitating the generation of high-complexity constructs. The ord...

DNA ligases are key enzymes in molecular and synthetic biology that catalyze the joining of breaks in duplex DNA and the end-joining of DNA fragments. Ligation fidelity (discrimination against the ligation of substrates containing mismatched base pairs) and bias (preferential ligation of particular sequences over others) have been well-studied in t...

The last years have witnessed the development of whole-genome cloning and transplantation methods and the complete synthesis of entire chromosomes. Recently, the first minimal cell, Mycoplasma mycoides JCVI-syn3.0, was created. Despite these milestone achievements, several questions remain to be answered. For example, is the composition of minimal...

Importance: Mesoplasma florum constitutes an attractive model for systems biology, and for the development of a simplified cell chassis in synthetic biology. M. florum is closely related to the mycoides cluster of mycoplasmas that has become a model for whole-genome cloning, genome transplantation, and genome minimization. However, M. florum shows...

Optimized hardware for propagating and checking software-programmable metadata tags can achieve low runtime overhead. We generalize prior work on hardware tagging by considering a generic architecture that supports software-defined policies over metadata of arbitrary size and complexity; we introduce several novel microarchitectural optimizations t...

We introduce the Programmable Unit for Metadata Processing (PUMP), a novel software-hardware element that allows flexible computation with uninterpreted metadata alongside the main computation with modest impact on runtime performance (typically 10--40% for single policies, compared to metadata-free computation on 28 SPEC CPU2006 C, C++, and Fortra...

Referencing outside the bounds of an array or buffer is a common source of bugs and security vulnerabilities in today's software. We can enforce spatial safety and eliminate these violations by inseparably associating bounds with every pointer (fat pointer) and checking these bounds on every memory access. By further adding hardware-managed tags to...

Mesoplasma florum is a small-genome fast-growing mollicute that is an attractive model for systems and synthetic genomics studies. We report the complete 825,824-bp genome sequence of a second representative of this species, M. florum strain W37, which contains 733 predicted open reading frames and 35 stable RNAs.

Hardware interlocks that enforce semantic invariants and allow fine-grained privilege separation can be built with reasonable costs given modern semiconductor technology. In the common error-free case, these mechanisms operate largely in parallel with the intended computation, monitoring the semantic intent of the computation on an operation-by-ope...

Safe is a clean-slate design for a secure host architecture. It integrates advances in programming languages, operating systems, and hardware and incorporates formal methods at every step. Though the project is still at an early stage, we have assembled a set of basic architectural choices that we believe will yield a high-assurance system. We sket...

An underlying goal of synthetic biology is to make the process of engineering biological systems easier and more reliable. In support of this goal, we developed BioBrick assembly standard 10 to enable the construction of systems from standardized genetic parts. The BioBrick standard underpins the distributed efforts by the synthetic biology researc...

A goal of synthetic biology is to make biological systems easier to engineer. One of the aims is to design, with nanometer-scale precision, biomaterials with well-defined properties. The surface-layer protein SbpA forms 2D arrays naturally on the cell surface of Lysinibacillus sphaericus, but also as the purified protein in solution upon the additi...

Table S1 - BioScaffold designs for maximal excision (see additional file). Several Type IIB enzyme recognition sites are aligned to the scar sequence TACTAGAK to determine maximum excision to the left and to the right of the BioScaffold. The alignment of the recognition sites to the scar fixes the sequence at the start and end of the BioScafffold....

BioBrick standard biological parts are designed to make biological systems easier to engineer (e.g. assemble, manipulate, and modify). There are over 5,000 parts available in the Registry of Standard Biological Parts that can be easily assembled into genetic circuits using a standard assembly technique. The standardization of the assembly technique...

Controlling RNA splicing opens up possibilities for the synthetic biologist. The Tetrahymena ribozyme is a model group I self-splicing ribozyme that has been shown to be useful in synthetic circuits. To create additional splicing ribozymes that can function in synthetic circuits, we generated synthetic ribozyme variants by rationally mutating the T...

This standard defines the required sequence properties for a Biobrick(tm) standard biological part. It does not define any functional characteristics of the parts, nor does it motivate any aspect of these standards. All sequences defined herein are specified in the 5' to 3' direction.

This standard defines the required sequence properties for a Biobrick(R) BB-2 standard biological part. It does not define any functional characteristics of the parts, nor does it motivate any aspect of these standards.

This BioBricks Foundation Request for Comments (BBF RFC) provides in- formation about the preparation and submission of BBF RFCs to The Bio- Bricks Foundation (BBF).

A key question in neuroscience is how memorization and association are supported by the mammalian cortex. One possible model, proposed by Valiant, uses sparse encodings in a sparse random graph, but the composability of operations in this model (e.g. an association triggering another association) has not previously been evaluated. We evaluate compo...

The underlying goal of synthetic biology is to make the process of engineering biological systems easier. Recent work has focused on defining and developing standard biological parts. The technical standard that has gained the most traction in the synthetic biology community is the BioBrick standard for physical composition of genetic parts. Parts...

ABSTRACT: BACKGROUND: The underlying goal of synthetic biology is to make the process of engineering biological systems easier. Recent work has focused on defining and developing standard biological parts. The technical standard that has gained the most traction in the synthetic biology community is the BioBrick standard for physical composition of...

Two-dimensional crystallization on lipid monolayers is a versatile tool to obtain structural information of proteins by electron microscopy. An inherent problem with this approach is to prepare samples in a way that preserves the crystalline order of the protein array and produces specimens that are sufficiently flat for high-resolution data collec...

Poster presented at Synthetic Biology 3.0: The third international conference in synthetic biology. Implementing in vivo information processing is a key challenge in synthetic biology. We describe the construction and characterization of digital transcription-based devices from zinc fingers and leucine zippers. We also present a framework around de...

Many important applications are organized around long-lived, irregular sparse graphs (e.g., data and knowledge bases, CAD optimization, numerical problems, simulations). The graph structures are large, and the applications need regular access to a large, data-dependent portion of the graph for each operation (e.g., the algorithm may need to walk th...

Poster presented at the 2005 ICSB meeting, held at Harvard Medical School in Boston, MA. The goal of Synthetic Biology is to engineer systems from biological parts. One class of systems are those whose purpose is to process information. My work seeks to build transcription-based devices for use in combinational digital logic. Preliminary characteri...

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1983. MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING Bibliography: leaves 100-106. by Thomas F. Knight, Jr. Ph.D.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1979. MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING Bibliography: leaves 49-50. by Thomas F. Knight, Jr. M.S.

Mol Syst Biol. 1: 2005.0020 A Scientist discovers that which exists. An Engineer creates that which never was.Theodore von Karman Biology will never be the same. The remarkable scientific success of biology in describing, explaining, and manipulating natural systems is so well recognized as to be a cliche–but the engineering application of that s...

Genomic DNA sequence data for the 16S rRNA gene and the gyrB gene of Mesoplasma pleciae PS-1(T) (=ATCC 49582(T)=NBRC 100476(T)) demonstrate a much closer relationship to Acholeplasma laidlawii and Acholeplasma oculi than to other species in the order Entomoplasmatales. In addition, the preferred use of UGG rather than UGA as the codon for tryptopha...

Banyan networks comprise a large class of networks that have been used for interconnection in large-scale multiprocessors and telephone switching systems. Regular variants of Banyan networks, such as delta and butterfly networks, have been used in multiprocessors such as the IBM RP3 and the BBN Butterfly. Analysis of the performance of Banyan netwo...

The existing teletype logic for the PDP-6 has been modified to accommodate up to four additional teletypes. These were added with a minimum of change to the existing logic, and are easily removable by taking out the cable in 4M2 and replacing the cable in 4M1 with the jumper module.

The CADR machine, a revised version of the CONS machine, is a general-purpose, 32-bit microprogrammable processor which is the basis of the Lisp-machine system, a new computer system being developed by the Laboratory as a high-performance, economical implementation of Lisp. This paper describes the CADR processor and some of the associated hardware...

We propose to develop a computer aided design tool which can help an engineer deal with system evolution from the initial phases of design right through the testing and maintenance phases. We imagine a design system which can function as a junior assistant. It provides a total conversational and graphical environment. It remembers the reasons for d...

Progress in molecular electronics is beginning to yield the technology for creating structures that incorporate myriads of nanoscale computationally active units. These could be fabricated at almost no cost, provided (1) the individual units need not all work correctly; and (2) there is no need to manufacture precise geometrical arrangements of the...

A separable electromagnetic coupler was designed, simulated, fabricated, and tested as part of a prototype eight-module multidrop memory bus. The coupler consists of broadside coupled traces, one on a rigid motherboard and the other on a flex circuit soldered to a daughter card. The zig-zag geometry of the traces reduces variation in the coupling c...

A separable electromagnetic coupler was designed, simulated, fabricated, and tested as part of a prototype eight module multidrop memory bus running at 1.6 Gb/s per differential pair. The coupler consists of broadside coupled traces, one on a rigid motherboard and the other on a flex circuit soldered to a daughter card. The zigzag geometry of the t...

The absurdity of the notion that a single real number can capture an infinite amount of information strongly motivates the search for models of physics where the information content of small regions of space‐time is finite. The rejection of the continuum is one such approach, in which space is viewed as a cellular automation with fixed rules captur...

AC coupling and pulse modulation are presented for high speed multidrop busses. A prototype eight module memory bus operates at a 400MHz symbol rate with 4 bits of modulated data per symbol, for 1.6Gb/s/pair. Test chips in 0.25μm 3M CMOS dissipate 40mW peak and occupy 340×200μm per pair.

Over the years there has been an enormous amount of hardware research in parallel computation. It os a testament...

ters [Carter94]. A guarded pointer is an unforgeable capability [Fabry74] with all relevant permission and segment size bits contained in the pointer itself (we will use the term segment to denote an allocated block of memory and object to denote data within a segment). Since user programs are not permitted to create capabilities, this allows the u...

Forwarding pointers allow safe and efficient data migration. However, they also introduce a new source of aliasing and as a result can have a serious impact on program performance. In this paper we introduce short quasi-unique ID's (squids), a simple hardware mechanism for capability architectures that mitigates the problems associated with aliasin...

Data placement is an extremely important issue in parallel machines. In order to obtain good performance, it is often necessary to distribute a single object (such as a large array) across many nodes in a system. Traditional mechanisms for achieving this distribution are expensive as they require the mapping from virtual addresses to physical locat...

The furious pace of Moore's Law is driving computer architecture into a realm where the the speed of light is the dominant factor in system latencies. The number of clock cycles to span a chip are increasing, while the number of bits that can be accessed within a clock cycle is decreasing. Hence, it is becoming more difficult to hide latency. One a...

Low-latency communication in large-scale multiprocessors requires highperformance interconnection schemes. Multistage interconnection networks with redundant paths combine high performance with fault-tolerance, but exact evaluation of the blocking probabilityofinterconnection networks with redundant paths is expensive. Equations for the blocking pr...

been used for interconnection in large-scale multiprocessors and telephone switching systems. Regular variants of Banyan networks, such as delta and butterfly networks, have been used in multiprocessors such as the IBM RP3 and the BBN Butterfly.

As the size of digital systems increases, the mean time between single component failures diminishes. To avoid component related failures, large computers must be fault-tolerant. In this paper, we focus on methods for achieving a high degree of fault-tolerance in multistage routing networks. We describe a multipath scheme for providing end-to-end f...

Conventional parallel computer architectures do not provide support for non-uniformly distributed objects. In this thesis, I introduce sparsely faceted arrays (SFAs), a new lowlevel mechanism for naming regions of memory, or facets, on different processors in a distributed, shared memory parallel processing system. Sparsely faceted arrays address t...

As parallel machines scale to one million nodes and beyond, it becomes increasingly difficult to build a reliable network that is able to guarantee packet delivery. Eventually large systems will need to employ fault-tolerant messaging protocols that afford correct execution in the presence of a lossy network. In this paper we present a lightweight...

As parallel machines scale to one million nodes and beyond, it becomes increasingly difficult to build a reliable network that is able to guarantee packet delivery. Eventually large systems will need to employ fault-tolerant messaging protocols that afford correct execution in the presence of a lossy network. In this paper we present a lightweight...

The objective of this research is to create the architectural, algorithmic, and technological foundations for exploiting programmable materials. These are materials that incorporate vast numbers of programmable elements that react to each other and to their environment. Such materials can be fabricated economically, provided that the computing elem...

Amorphous computing is the development of organizational principles and programming languages for obtaining coherent behaviors from the cooperation of myriads of unreliable parts that are interconnected in unknown, irregular, and time-varying ways. The impetus for amorphous computing comes from developments in microfabrication and fundamental biolo...

We previously introduced the length-only discrimination (LOD) method for generate and search models of DNA computing. Here we report experimental confirmation of the validity of the basic operations of LOD method. We created a test graph consisting of four nodes and three edges, in which multiple paths are possible. Experimental results indicate th...

Multicellular organisms create complex patterned structures from identical, unreliable components. Learning how to engineer such robust behavior is important to both an improved understanding of computer science and to a better understanding of the natural developmental process. Earlier work by our colleagues and ourselves on amorphous computing de...

We propose a biochemically plausible mechanism for constructing digital logic signals and gates of significant complexity within living cells. These mechanisms rely largely on co-opting existing biochemical machinery and binding proteins found naturally within the cell, replacing difficult protein engineering problems with more straightforward engi...

We present techniques for combining high-performance computing with feedback to enable the correction of imperfections in the alignment, optical system, and fabrication of very high-resolution display devices. The key idea relies on the measurement of relative alignment, rotation, optical distortion, and intensity gradients of an aggregated set of...

Inter-chip signaling latency and bandwidth can be key factors limiting the performance of large VLSI systems. We present a high performance, transmission line signaling scheme for point-to-point communications between VLSI components. In particular, we detail circuitry which allows a pad driver to sense the voltage level on the attached pad during...

. We propose a mapping from digital logic circuits into genetic regulatory networks with the following property: the chemical activity of such a genetic network in vivo implements the computation specified by the corresponding digital circuit. Logic signals are represented by the synthesis rates of cytoplasmic DNA binding proteins. Gates consist of...

The ability to display high-resolution images is a requisite of widespread use of high-bandwidth portable information devices. Liquid-crystal-on-silicon (LCOS) technology enables same-die integration of control circuitry and display for substantial overall system power reduction. This 160×120 LCOS microdisplay uses 25 μm pixels based on a 0.8 μm 3-...

Clock distribution is an important issue in digital design. Engineers want to distribute a square-wave with low skew and fast transition times across very wide chips and they want to do so, wasting as little power as possible. This paper describes a new clock distribution technique utilizing resonant transmission lines that not only reduces clock s...

Although a complete nanotechnology does not yet exist, we can already foresee some new directions in theoretical computer science that will be required to help us design maximally efficient computers using nanoscale components. In particular, we can devise novel theoretical models of computation that are intended to faithfully reflect the computati...

Reversibility is the only way to compute with asymptotically zero power, and is a novel approach to low power, low energy computing. Recent implementations of reversible and adiabatic [15, 7] logic in standard cmos silicon processes have motivated further research into reversible computing. The application of reversible computing techniques to redu...

Field-Programmable Gate Arrays (FPGAs) and Single-Instruction MultipleData (SIMD) processing arrays share many architectural features. In both architectures, an array of simple, fine-grained logic elements is employed to provide high-speed, customizable, bit-wise computation. In this paper, we present a unified computational array model which encom...

Inter-chip signaling latency and bandwidth can be key factors limiting the performance of large VLSI systems. We present a high performance, transmission line signaling scheme for point-to-point communications between VLSI components. In particular, we detail circuitry which allows a pad driver to sense the voltage level on the attached pad during...

The reversible and "adiabatic" transfer of charge in digital circuits has recently been a subject of interest in the low-power electronics community, but no one has yet created a complete, purely reversible CPU using this technology. Fundamental physical scaling laws imply that a fully-reversible processing element would permit unboundedly greater...

An important goal for computer science is to find practical, scalable models of computation that are as efficient as is permitted by the laws of physics. Given a constant upper bound on entropy density, physics implies fundamental constraints on the efficiency of any computation that produces entropy. As a result, it appears that the most efficient...

. The reversible and "adiabatic" transfer of charge in digital circuits has recently been a subject of interest in the low-power electronics community, but no one has yet created a complete, purely reversible CPU using this technology. Fundamental physical scaling laws imply that a fully-reversible processing element would permit unboundedly greate...

The Multipath Enhanced Transit Router Organization (METRO) is a flexible routing architecture for high-performance, tightly-coupled, multiprocessors and routing hubs. A METRO router is a dilated cross-bar routing component supporting half-duplex bidirectional, pipelined, circuit-switched connections. Each METRO router is self-routing and supports d...

Multistage networks are important in a wide variety of applications. Expander-based networks, such as multibutterflies, are a tremendous improvement over traditional butterflies in both fault and congestion tolerance. However, multibutterflies cost at least twice as much in chips and wiring as butterflies. It is also impossible to build large multi...

Nearly all of the conductors interconnecting a die to a substrate can and should be replaced by capacitor junctions. Capacitive coupling is a new approach for mechanically and electrically packaging electronic modules, and provides order-of-magnitude decreases in manufacturing and repair costs, extremely tight junction pitch, lower power, higher sp...

Describes the Abacus machine at a number of levels. Presents the microarchitecture of the PE comprising the reconfigurable bit-parallel array, a set of arithmetic and communication primitives, details of the VLSI implementation, and system-level design issues of a high-speed SIMD array. The most concrete goal of the Abacus project was to design and...

This paper described the Abacus machine at a number of levels. We presented the microarchitecture of the PE comprising the reconfigurable bit-parallel array, a set of arithmetic and communication primitives, details of the VLSI implementation, and system-level design issues of a high-speed SIMD array. The most concrete goal of the Abacus project wa...

Important improvements in network bandwidth, latency, and fault tolerance can be provided by careful selection of the protocols, choice of network topology, details of interconnection wiring, and basic wire driving technologies. We examine the improvements in some of these areas as part of the Transit project at the MIT Artificial Intelligence Labo...

Multistage networks are important in a wide variety of applications. Expander-based networks, such as multibutterflies, are a tremendous improvement over traditional butterflies in both fault and congestion tolerance. However, multibutterflies cost at least twice as much in chips and wiring as butterflies. It is also impossible to build large multi...

Energy dissipation of CMOS circuits is becoming a major concern in the design of digital systems. Earlier, we presented a new form of CMOS charge recovery logic (SCRL), with an energy dissipation per operation that falls linearly with operating frequency, as opposed to the constant energy required for conventional CMOS circuits. These SCRL circuits...

In this paper, we look beyond conductive coupling to the fundamental opportunity for passing signals between chips by non-conductive means. Capacitively coupled interconnects afford a number of advantages over conventional, conductive junctions in flipped chip MCM designs. The main focus of this paper is to describe a conceptual design for a switch...

Capacitive coupling of off-chip interconnects offers a number of advantages, including low manufacturing and repair costs, dense form factors, low power, high speed, extremely high junction pitch, and easy testing. In this paper, we review and compare the practicalities of conductive and capacitive coupling, and discuss novel issues of manufacturab...