Scientific production

Here we list the most significant 20% of publications by the members of the CRI Collaboratory (UMR U1284), organized following the our main research themes. Full list will be made available shortly.

Selected publications

Articles

(I) Systems Engineering and Evolution Dynamics of Cooperation traits

  1. Dimitriu T, Misevic D, Lotton C, Brown SP, Lindner AB, Taddei F (2016). Indirect Fitness Benefits Enable the Spread of Host Genes Promoting Costly Transfer of Beneficial Plasmids. PLoS Biol. 2016 Jun 7;14(6):e1002478.

  2. Dimitriu T, Lotton C, Bénard-Capelle J, Misevic D, Brown SP, Lindner AB, Taddei F (2014) Genetic information transfer promotes cooperation in bacteria. Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):11103-8. doi: 10.1073/pnas.1406840111.

The two papers above provide an explanation for the prevalence of cooperative genes on mobile elements, and suggest a previously unidentified benefit of horizontal gene transfer for bacteria. The effect is the strongest when public good genes undergo epidemics dynamics, making horizontal transfer especially relevant for pathogenic bacteria that repeatedly infect new hosts and base their virulence on costly public goods.

(II) Systems Engineering and Evolution Dynamics of senescence

  1. Chen P, Xu L, Liu J, Hol FJ, Keymer JE, Taddei F, Han D, Lindner AB*. Nanoscale probing the kinetics of oriented bacterial cell growth using atomic force microscopy. Small. 2014 Aug 13;10(15):3018-25. The paper demonstrates our capacity to engineer tailored microfluidics, here applied for first in vivo AFM time lapse of growing untreated wild-type bacterial cells.
  2. Coquel AS, Jacob JP, Primet M, Demarez A, Dimiccoli M, Julou T, Moisan L, Lindner AB,=, Berry H,=,. Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect. PLoS Comput Biol. 2013 Apr;9(4):e1003038. doi: 10.1371/journal.pcbi.1003038.

This paper provides quantitative data and mathematical model to demonstrate that aging-related protein aggregates polar localization in E. coli results from coupling of passive diffusion-aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on macromolecular crowding) in diffusion-based protein localization in E. coli.

  1. Yang Y, Santos AL, Xu L, Taddei F, Lindner AB* (2018) Temporal scaling of ageing as an adaptive strategy of Escherichia coli. bioRxiv 376566; bioRxiv 376566; doi: https://doi.org/10.1101/376566 (Science Advances, in final revisions)

This work shows that the bacteria Escherichia coli follow the same death/hazard rate curve as humans, called the Gompertz Law. This is an important finding that tells us that the death rate curve that humans follow through their lifespan has been around since one of the very first living organisms that inhabited earth, although there are exceptions that need to be explained eventually. We also show that death and survival rates can be manipulated with increasing and/or decreasing the organisms stress response, much like humans´ longevity can be increased with a calorie-restricted diet, which increases the protective stress response.

(III) Open Synthetic biology to accelerate drug discovery against Tuberculosis

  1. Libis, V.K., Bernheim, A.G., Basier, C., Jaramillo-Riveri, S., Deyell, M., Aghoghogbe, I., Atanaskovic, I., Bencherif, A.C., Benony, M., Koutsoubelis, N., Löchner, A.C., Marinkovic, Z.S., Zahra, S., Zegman, Y., Lindner, A.B., Wintermute, E.H., 2014. Silencing of Antibiotic Resistance in E. coli with Engineered Phage Bearing Small Regulatory RNAs. ACS Synth. Biol. 3, 1003–1006. doi:10.1021/sb500033d

This research project was conducted exclusively with a team of undergraduate researchers from the Paris Bettencourt iGEM team. In 2013, the project was awarded the Grand Prize at the international Genetically Engineered Machines (iGEM) competition.

(IV) Gene expression patterns and gene regulatory networks in development

  1. Mora N, Oliva C, Fiers M, Ejsmont R, Soldano A, Zhang TT, Yan J, Claeys A, De Geest N, Hassan BA. A Temporal Transcriptional Switch Governs Stem Cell Division, Neuronal Numbers, and Maintenance of Differentiation. Dev Cell. 2018 This paper demonstrates a novel, time-sensitive regulatory mechanism of cell differentiation. Genes involved in this mechanism are also important in Drosophila eye specification - the current model that we work with in the lab.

(V) Modelling the growth of the actin cytoskeleton

  1. R. Kusters, H. Lin, R. Zandi, I. Tsvetkova, B. Dragnea, P. van der Schoot; Role of charge regulation and size polydispersity in nanoparticle encapsulation by viral coat proteins; The Journal of Physical Chemistry B (2015).

In this paper we present a model describing the encapsulation of spherical particles bearing weakly acidic surface groups and investigate how charge regulation and size polydispersity impact upon the encapsulation efficiency of gold nanoparticles by model coat proteins.

(VI) Perturbing the interactome: network impact and perturbation propagation in biology and personalized medicine

  1. M. Santolini, A-L Barabasi, (2018) Predicting perturbation patterns from the topology of biological networks. Proc Natl Acad Sci USA, 169, 201720589. Altmetric score: 147 (top 1% of all Altmetric scores). This paper is important in the Network medicine field as it provides a basis to quantify the importance of network topology in predicting the spread of perturbations (differential expression), without the need for sophisticated kinetic models.

  2. Kilic,A., Santolini,M., Nakano,T., Schiller,M., Teranishi,M., Gellert,P., Ponomareva,Y., Braun,T., Uchida,S., Weiss,S.T., et al. (2018) A systems immunology approach identifies the collective impact of 5 miRs in Th2 inflammation. JCI Insight, 3. The major result of this paper resides in the fact that by prioritizing miRNAs by their impact on the gene interaction network instead of differential expression, we uncover and validate novel targets involved in asthma.

  3. M. Santolini, C. Rau, S. Ren, J. Saucerman, J. Wang, J. Weiss, Y. Wang, A. Lu- sis, A. Karma. A personalized, multi-omics approach identifies genes involved in cardiac hypertrophy and heart failure. npj Systems Biology and Application, doi: 10.1038/s41540-018-0046-3, Feb 2018

In this paper, we use 100 genetically diverse strains of mice to disentangle genetic from environmental effect of a cardiac stressor. We developed a novel method to extract “personalised” genes that are missed by traditional population wide methods.

  1. M. Santolini, I. Sakakibara, M. Gauthier, V. Mouly, JP. Concordet, PA. Defossez, V. Hakim, P. Maire. MyoD reprogramming requires Six1 and Six4 homeoproteins: genome- wide cis-regulatory module analysis. Nucleic Acids Research, 10.1093/nar/gkw512, June 2016

This is an in-depth study exhibiting the synergy between Six and MyoD proteins taking place during myogenic differentiation, using bioinformatics tools developed during my PhD as well as extensive validation of 20 new enhancers and several novel transcription factor binding sites.

(VII) Brain evolution, development, and neurodevelopmental disorders

  1. Heuer K and Toro R (2018) Role of mechanical morphogenesis on the development and evolution of the neocortex. Accepted in Physics of Life Reviews. Preprint: https://doi.org/10.31219/osf.io/d2bgr This review extends our discussion about the role of mechanical morphogenesis in neocortical development into brain evolution.

  2. Foubet O, Trejo M, Toro R* (2018) Mechanical morphogenesis and the development of neocortical organisation. Cortex, https://doi.org/10.1016/j.cortex.2018.03.005.

This article develops our theoretical framework for the role of mechanical morphogenetic processes on the development of the neocortex. We aim at introducing physicists to the problematic of brain development, and neurobiologist to the formalisation of non-linear elasticity theory and the biomechanical modelling of growth.

  1. Di Martino A, O’Connor D, Chen B, Alaerts K, Anderson JS, Assaf A, Balsters JH, Baxter L, Beggiato A, Bernaerts S, Blanken LME, Bookheimer SY, Braden BB, Byrge LB, Castellanos FX, Dapretto M, Delorme R, Fair D, Fishman I, Fitzgerald J, Gallagher L, Keehn RJJ, Kennedy DP, Lainhart JE, Luna BL, Mostofsky SH, Müller RA, Nebel MB, Nigg JT, O’Hearn K, Solomon M, Toro R, Vaidya CJ, Wenderoth N, White T, Craddock RC, Lord C, Leventhal B, Milham MP. Enhancing studies of the connectome in autism using the autism brain imaging data exchange II. Scientific Data, https://doi.org/10.1038/sdata.2017.10

This article is the result of our participation into the 2nd installment of the ABIDE project. The production of this article required an important effort to find the legal and ethical framework that would allow French clinicians to share their data.

  1. Lefèvre A, Beggiato A, Bourgeron T, Toro R (2015) Neuroanatomical Diversity of Corpus Callosum and Brain Volume in Autism: Meta-analysis, Analysis of the Autism Brain Imaging Data Exchange Project, and Simulation. Biol Psychiatry, https://doi.org/10.1016/j.biopsych.2015.02.010. Preprint: https://doi.org/10.1101/002691

This analysis of the anatomy of the corpus callosum in autism is one of the first to use the open access ABIDE data. It provides negative evidence for the idea that the corpus callosum is smaller in patients with autism, and substantial evidence of lack of statistical power and publication bias in the previous literature.

  1. Hibar D. P., Stein J. L., Renteria M. E. , Arias-Vasquez A, Desrivières S, Jahanshad N, Toro R, et al. 2015. “Common Genetic Variants Influence Human Subcortical Brain Structures.” Nature, https://doi.org/10.1038/nature14101

This is the 2nd article of the ENIGMA consortium, a follow up of the original analyses proposed by the same analysis team. The sample is once again the largest ever studied, more than 30k subjects with brain imaging and genetics data, representing an important effort of international collaboration and coordination.

  1. Toro R, Poline JB, Huguet G, Loth E, Frouin V, Banaschewski T, Barker GJ, Bokde A, Büchel C, Carvalho FM, Conrod P, Fauth-Bühler M, Flor H, Gallinat J, Garavan H, Gowland P, Heinz A Ittermann B, Lawrence C, Lemaître H, Mann K, Nees F, Paus T, Pausova Z, Rietschel M, Robbins T, Smolka MN, Ströhle A, Schumann G, Bourgeron T and the IMAGEN consortium (2014) Genomic architecture of human neuroanatomical diversity. Mol Psychiatry, https://doi.org/10.1038/mp.2014.99. Preprint: https://doi.org/10.1101/001198

Until this article, imaging genetics analyses have looked for individual variants of strong effect (genome-wide significant). Here, I provide for the first time evidence of a strongly polygenic genomic architecture. The results have since been replicated and extended by several research groups.

  1. Husson A., Chevrier J., Maria Montessori meets gesture tracking technologies, MOCO conference, New Cross, London, United Kingdom, 28-30 June 2017 (MOCO’17), 3 pages. Proceedings Paper

This paper emphasizes the tracking technologies based on machine learning used to monitor gestures. This is the tool used in our collaboration on rehabilitation with Hopital Lariboisiere.

  1. Carpentier S, Rodrigues MS, Vitorino MV, Costa L, Charlaix E, Chevrier J*, Out of equilibrium anomalous elastic response of a water nano-meniscus Appl. Phys. Lett. 107, 204101 (2015) 2015, Carpentier S, Rodrigues MS, Charlaix E, Chevrier J, Proximity effect on hydrodynamic interaction between a sphere and a plane measured by force feedback microscopy at different frequencies, Applied Physics Letters

This is a physics paper based on research at UGA. It shows for the first time how it is possible to study the dynamics of a capillary nanobridge.

  1. Rodrigues MS, Costa L, Chevrier J, Comin F, System analysis of force feedback microscopy Journal of Applied Physics, Journal of Applied Physics 115, 054309 (2014); This reports on development on a new AFM mode which has full control of the nanotip in space. This enables one to separately measure displacement and force at nanoscale, i.e. to determine work done by the nanotip when interacting with a surface at nanoscale.

A method for molecular dynamics on curved surfaces; S. Paquay, R. Kusters; Biophysical Journal (2016): We combined standard constraint algorithms with the classical velocity Verlet scheme to perform molecular dynamics simulations of particles constrained to an arbitrarily curved surface and developed it as an open source package for LAMMPS, a MD software package.

Review articles

Review articles

  • M. Adrian, R. Kusters, C. Wierenga, C. Storm, C. Hoogenraad, L. Kapitein; Barriers in the brain: resolving dendritic spine morphology and compartmentalization;Frontiers in Neuroanatomy (2014)

  • Santos AL, Sinha S, Lindner AB. The Good, the Bad, and the Ugly of ROS: New Insights on Aging and Aging-Related Diseases from Eukaryotic and Prokaryotic Model Organisms (2018). Oxid Med Cell Longev. 2018 Mar 18;2018:1941285. doi:10.1155/2018/1941285.

  • Santos AL, Lindner AB. Protein Posttranslational Modifications: Roles in Aging and Age-Related Disease. Oxid Med Cell Longev. 2017;2017:5716409. Doi: 10.1155/2017/5716409.

  • Ejsmont RK, Hassan BA. The Little Fly that Could: Wizardry and Artistry of Drosophila Genomics. Genes (Basel). 2014
Books

Books

  • F Taddei (2018) Apprendre au XXIème Siècle. Edition Calmann Lévy
  • Y Yang, X Song, AB Lindner (2016) Time-lapse microscopy and image analysis of Escherichia coli cells in mother machines, Methods in Microbiology, Vol 43, chap. 2, 49-68, Elsevier.