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James J. Collins

Bio: James J. Collins is an academic researcher from Massachusetts Institute of Technology. The author has contributed to research in topics: Synthetic biology & Population. The author has an hindex of 151, co-authored 669 publications receiving 89476 citations. Previous affiliations of James J. Collins include Baylor College of Medicine & University at Albany, SUNY.


Papers
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Journal ArticleDOI
Emily C. Oates1, Emily C. Oates2, Emily C. Oates3, Kristi J. Jones3, Sandra Donkervoort4, Amanda Charlton3, Susan Brammah5, John E. Smith6, James S. Ware7, Kyle S. Yau8, Lindsay C. Swanson9, Nicola Whiffin7, Anthony Peduto3, Anthony Peduto10, Adam Bournazos3, Leigh B. Waddell3, Michelle A. Farrar2, Michelle A. Farrar11, Hugo Sampaio2, Hugo Sampaio11, Hooi Ling Teoh2, Hooi Ling Teoh11, Phillipa J. Lamont12, David Mowat2, David Mowat11, Robin B. Fitzsimons, Alastair Corbett5, Monique M. Ryan13, Monique M. Ryan14, Gina L. O'Grady3, Sarah A. Sandaradura3, Roula Ghaoui3, Himanshu Joshi3, Jamie L. Marshall15, Jamie L. Marshall9, Melinda A. Nolan, Simranpreet Kaur3, Jaya Punetha16, Jaya Punetha17, Ana Töpf18, E. Harris18, Madhura Bakshi2, Casie A. Genetti9, M. Marttila9, Ulla Werlauff, Nathalie Streichenberger19, Alan Pestronk20, Ingrid Mazanti, Jason Pinner21, Carole Vuillerot22, Carla Grosmann23, Ana Camacho, Payam Mohassel4, M. Leach4, A. Reghan Foley4, Diana Bharucha-Goebel4, Diana Bharucha-Goebel16, James J. Collins, Anne M. Connolly20, Heather R. Gilbreath24, Susan T. Iannaccone, Diana Castro, Beryl B. Cummings15, Beryl B. Cummings9, Richard Webster3, L. Lazaro, John Vissing25, Sandra Coppens26, Nicolas Deconinck26, Ho Ming Luk, Neil H. Thomas, Nicola C. Foulds, Marjorie A. Illingworth, Sian Ellard27, Catriona McLean, Rahul Phadke28, Gianina Ravenscroft8, Nanna Witting25, Peter Hackman29, Isabelle Richard, Sandra T. Cooper3, Erik-Jan Kamsteeg30, Eric P. Hoffman17, Eric P. Hoffman16, Kate Bushby18, Volker Straub18, Bjarne Udd, Ana Ferreiro31, Kathryn N. North3, Kathryn N. North14, Nigel F. Clarke3, Monkol Lek9, Monkol Lek15, Alan H. Beggs9, Carsten G. Bönnemann4, Daniel G. MacArthur15, Daniel G. MacArthur9, Henk Granzier, Mark R. Davis, Nigel G. Laing8 
TL;DR: Comprehensive clinical characterization of congenital titinopathy is presented to facilitate diagnosis and management of this important emerging disorder.
Abstract: OBJECTIVE: Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management of this important emerging disorder. METHODS: Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans. We then undertook a detailed analysis of the clinical, histopathological and imaging features of these patients. RESULTS: All patients had prenatal or early onset hypotonia and/or congenital contractures. None had ophthalmoplegia. Scoliosis and respiratory insufficiency typically developed early and progressed rapidly, whereas limb weakness was often slowly progressive, and usually did not prevent independent walking. Cardiac involvement was present in 46% of patients. Relatives of 2 patients had dilated cardiomyopathy. Creatine kinase levels were normal to moderately elevated. Increased fiber size variation, internalized nuclei and cores were common histopathological abnormalities. Cap-like regions, whorled or ring fibers, and mitochondrial accumulations were also observed. Muscle magnetic resonance imaging showed gluteal, hamstring and calf muscle involvement. Western blot analysis showed a near-normal sized titin protein in all samples. The presence of 2 mutations predicted to impact both N2BA and N2B cardiac isoforms appeared to be associated with greatest risk of cardiac involvement. One-third of patients had 1 mutation predicted to impact exons present in fetal skeletal muscle, but not included within the mature skeletal muscle isoform transcript. This strongly suggests developmental isoforms are involved in the pathogenesis of this congenital/early onset disorder. INTERPRETATION: This detailed clinical reference dataset will greatly facilitate diagnostic confirmation and management of patients, and has provided important insights into disease pathogenesis. Ann Neurol 2018;83:1105-1124.

75 citations

01 Oct 2017
TL;DR: A CRISPR–Cas9-based gene drive array platform is developed and combined with mating-competent Candida albicans haploids to generate homozygous double-deletion mutants, transforming the ability to do genetic interaction analyses in fungi.
Abstract: Candida albicans is the leading cause of fungal infections; yet, complex genetic interaction analysis remains cumbersome in this diploid pathogen. Here, we developed a CRISPR-Cas9-based 'gene drive array' platform to facilitate efficient genetic analysis in C. albicans. In our system, a modified DNA donor molecule acts as a selfish genetic element, replaces the targeted site and propagates to replace additional wild-type loci. Using mating-competent C. albicans haploids, each carrying a different gene drive disabling a gene of interest, we are able to create diploid strains that are homozygous double-deletion mutants. We generate double-gene deletion libraries to demonstrate this technology, targeting antifungal efflux and biofilm adhesion factors. We screen these libraries to identify virulence regulators and determine how genetic networks shift under diverse conditions. This platform transforms our ability to perform genetic interaction analysis in C. albicans and is readily extended to other fungal pathogens.

75 citations

Journal ArticleDOI
TL;DR: It is shown that the fluctuation-dissipation theorem can be applied to the human postural control system and that the dynamic response of the postural system to a weak mechanical perturbation can be predicted from the fluctuations exhibited by the system under quasistatic conditions.
Abstract: During quiet standing, the human body sways in a stochastic manner. Here we show that the fluctuation-dissipation theorem can be applied to the human postural control system. That is, the dynamic response of the postural system to a weak mechanical perturbation can be predicted from the fluctuations exhibited by the system under quasistatic conditions. We also show that the estimated correlation and response functions can be described by a simple stochastic model consisting of a pinned polymer. These findings suggest that the postural control system utilizes the same control mechanisms under quiet-standing and dynamic conditions. [S0031-9007(97)05009-6]

75 citations

Journal ArticleDOI
TL;DR: The spectrum of causative genes in extracellular matrix (ECM)-related myopathies be extended to include COL12A1, a member of the FACIT collagens (fibril-associated collagen with interrupted triple helices) in five individuals from two families showing dominant inheritance with a clinical phenotype resembling classical BM.
Abstract: Bethlem myopathy (BM) [MIM 158810] is a slowly progressive muscle disease characterized by contractures and proximal weakness, which can be caused by mutations in one of the collagen VI genes (COL6A1, COL6A2 and COL6A3). However, there may be additional causal genes to identify as in ∼50% of BM cases no mutations in the COL6 genes are identified. In a cohort of -24 patients with a BM-like phenotype, we first sequenced 12 candidate genes based on their function, including genes for known binding partners of collagen VI, and those enzymes involved in its correct post-translational modification, assembly and secretion. Proceeding to whole-exome sequencing (WES), we identified mutations in the COL12A1 gene, a member of the FACIT collagens (fibril-associated collagens with interrupted triple helices) in five individuals from two families. Both families showed dominant inheritance with a clinical phenotype resembling classical BM. Family 1 had a single-base substitution that led to the replacement of one glycine residue in the triple-helical domain, breaking the Gly-X-Y repeating pattern, and Family 2 had a missense mutation, which created a mutant protein with an unpaired cysteine residue. Abnormality at the protein level was confirmed in both families by the intracellular retention of collagen XII in patient dermal fibroblasts. The mutation in Family 2 leads to the up-regulation of genes associated with the unfolded protein response (UPR) pathway and swollen, dysmorphic rough-ER. We conclude that the spectrum of causative genes in extracellular matrix (ECM)-related myopathies be extended to include COL12A1.

75 citations

Journal ArticleDOI
TL;DR: In this paper, a synthetic genetic feedback controller dynamically steers the concentration of a gene regulatory network's key transcription factors to any desired value, by adjusting TF expression based on the discrepancy between desired and actual TF concentrations.
Abstract: To artificially reprogram cell fate, experimentalists manipulate the gene regulatory networks (GRNs) that maintain a cell's phenotype. In practice, reprogramming is often performed by constant overexpression of specific transcription factors (TFs). This process can be unreliable and inefficient. Here, we address this problem by introducing a new approach to reprogramming based on mathematical analysis. We demonstrate that reprogramming GRNs using constant overexpression may not succeed in general. Instead, we propose an alternative reprogramming strategy: a synthetic genetic feedback controller that dynamically steers the concentration of a GRN's key TFs to any desired value. The controller works by adjusting TF expression based on the discrepancy between desired and actual TF concentrations. Theory predicts that this reprogramming strategy is guaranteed to succeed, and its performance is independent of the GRN's structure and parameters, provided that feedback gain is sufficiently high. As a case study, we apply the controller to a model of induced pluripotency in stem cells.

73 citations


Cited by
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04 Jun 1998-Nature
TL;DR: Simple models of networks that can be tuned through this middle ground: regular networks ‘rewired’ to introduce increasing amounts of disorder are explored, finding that these systems can be highly clustered, like regular lattices, yet have small characteristic path lengths, like random graphs.
Abstract: Networks of coupled dynamical systems have been used to model biological oscillators, Josephson junction arrays, excitable media, neural networks, spatial games, genetic control networks and many other self-organizing systems. Ordinarily, the connection topology is assumed to be either completely regular or completely random. But many biological, technological and social networks lie somewhere between these two extremes. Here we explore simple models of networks that can be tuned through this middle ground: regular networks 'rewired' to introduce increasing amounts of disorder. We find that these systems can be highly clustered, like regular lattices, yet have small characteristic path lengths, like random graphs. We call them 'small-world' networks, by analogy with the small-world phenomenon (popularly known as six degrees of separation. The neural network of the worm Caenorhabditis elegans, the power grid of the western United States, and the collaboration graph of film actors are shown to be small-world networks. Models of dynamical systems with small-world coupling display enhanced signal-propagation speed, computational power, and synchronizability. In particular, infectious diseases spread more easily in small-world networks than in regular lattices.

39,297 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: In this paper, a simple model based on the power-law degree distribution of real networks was proposed, which was able to reproduce the power law degree distribution in real networks and to capture the evolution of networks, not just their static topology.
Abstract: The emergence of order in natural systems is a constant source of inspiration for both physical and biological sciences. While the spatial order characterizing for example the crystals has been the basis of many advances in contemporary physics, most complex systems in nature do not offer such high degree of order. Many of these systems form complex networks whose nodes are the elements of the system and edges represent the interactions between them. Traditionally complex networks have been described by the random graph theory founded in 1959 by Paul Erdohs and Alfred Renyi. One of the defining features of random graphs is that they are statistically homogeneous, and their degree distribution (characterizing the spread in the number of edges starting from a node) is a Poisson distribution. In contrast, recent empirical studies, including the work of our group, indicate that the topology of real networks is much richer than that of random graphs. In particular, the degree distribution of real networks is a power-law, indicating a heterogeneous topology in which the majority of the nodes have a small degree, but there is a significant fraction of highly connected nodes that play an important role in the connectivity of the network. The scale-free topology of real networks has very important consequences on their functioning. For example, we have discovered that scale-free networks are extremely resilient to the random disruption of their nodes. On the other hand, the selective removal of the nodes with highest degree induces a rapid breakdown of the network to isolated subparts that cannot communicate with each other. The non-trivial scaling of the degree distribution of real networks is also an indication of their assembly and evolution. Indeed, our modeling studies have shown us that there are general principles governing the evolution of networks. Most networks start from a small seed and grow by the addition of new nodes which attach to the nodes already in the system. This process obeys preferential attachment: the new nodes are more likely to connect to nodes with already high degree. We have proposed a simple model based on these two principles wich was able to reproduce the power-law degree distribution of real networks. Perhaps even more importantly, this model paved the way to a new paradigm of network modeling, trying to capture the evolution of networks, not just their static topology.

18,415 citations

Journal ArticleDOI
TL;DR: In this paper, Imagined communities: Reflections on the origin and spread of nationalism are discussed. And the history of European ideas: Vol. 21, No. 5, pp. 721-722.

13,842 citations

Journal ArticleDOI
Stephen S Lim1, Theo Vos, Abraham D. Flaxman1, Goodarz Danaei2  +207 moreInstitutions (92)
TL;DR: In this paper, the authors estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010.

9,324 citations