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  Constraints on the cell chassis
 

   

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Epigenesis: cognition, immunology and epidemiology


JP Changeux, P Courrège, A Danchin
A theory of the epigenesis of neuronal networks by selective stabilization of synapses
Proc Natl Acad Sci U S A (1973) 70: 2974-2978 pubmedpnas pdf

JP Changeux, A Danchin
Selective stabilisation of developing synapses as a mechanism for the specification of neuronal networks
Nature (1976) 264: 705-712 pubmed

The dialogue between preformation and epigenesis is at the core of life. A construction rule is what is transmitted through heredity. This rule offers multiple choices. This can be seen most easily in the nervous system, the blood system or the immune system. The interaction with the environment (which cannot be the same for two individuals), leads to the selection, by a stabilisation process (ensuring perennity) of a fraction of what has been offered initially as choices. This is the basis for learning, as well as for the generation of identity
 
Le dialogue entre préformation et épigenèse est au cœur de la vie. Ce qui est transmis de façon héréditaire et stable, est une règle de mise en place. Cette règle a la particularité d'offrir des choix multiples. Cela se remarque aussi bien dans le système nerveux, que le système circulatoire ou le système immunitaire. L'interaction  avec l'environnement (qui ne peut être le même pour deux individus), conduit à la sélection, par stabilisation (simple pérennité) d'une partie de ce qui a été offert initialement. On a là la base de l'apprentissage, et de la genèse de l'identité

A Danchin
A selective theory for the epigenetic specification of the monospecific antibody production in single cell lines
Ann Immunol (Paris) (1976) 127: 787-804 pubmed

uk-flagIn the selective model presented a command from the environment permits selection of a network of antibodies that respond to environmental cues. The core of the model is the idea that one needs to "make room" for accumulating objects (here antibodies) that have increased their information content as the consequence of their interaction with the environment
 
fr-flag Dans le modèle sélectif ici présenté une commande de l'environnement permet la sélection d'un réseau d'anticorps qui répondent à un stimulus extérieur. Le principe du modèle est l'idée qu'il faut "faire de la place" pour accumuler des objets (ici des anticorps) qui ont une information qui s'accroît progressivement en fonction de l'interaction avec le milieu

fr A Danchin
Stabilisation fonctionnelle et épigenèse: une approche biologique de la genèse de l'identité individuelle
In: "L'Identité" (JM Benoist, ed) Grasset (1977): 185-221

uk-flagIndividual identity results from the overlap of three processes unfolding at different time and space scales, phylogeny, ontogeny and epigenesis. It is created by the formation and destruction of relationships, and this makes emerge behaviours and forms that are, by construction, unpredictable and new. Thus the word of the poet Arthur Rimbaud "I is an Other" takes it flesh in all identities
 
fr-flagL'individu résulte de la superposition de trois processus se déroulant à des échelles différentes, la phylogenèse, l'ontogenèse et l'épigenèse. Il se crée par la formation et la destruction de relations, et cela fait apparaître des formes et des comportements par construction imprévisibles. Ainsi le mot du poète "Je est un Autre" s'incarne

A Danchin
The specification of the immune response: a general selective model
Mol Immunol (1979) 16: 515-526 pubmed

fr JP Changeux, P Courrège, A Danchin, JM Lasry
Un mécanisme biochimique pour l'épigenèse de la jonction neuro-musculaire
C R Séances Acad Sci III (1981) 292: 449-453 pubmed

TW Ng, G Turinici, A Danchin
A double epidemic model for the SARS propagation
BMC Infect Dis (2003) 3: 19 pubmed BMC

TW Ng, G Turinici, WK Ching, SK Chung, A Danchin
A parasite vector-host epidemic model for TSE propagation
Medical Science Monitor (2007) 13: 59-66 pubmed pdf

A Danchin, A Sekowska
The role of information in evolutionary genomics of bacteria
In: Evolutionary genomics and systems biology (G Caetano-Anollés, Editor), Wiley & sons, Hoboken, NJ (2010) pp 81-94
biosapiens probactys
  evolution

 

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Philosophy of Synthetic Biology: epistemology, ethics, history of sciences

A Danchin
The tree and the ring. Hierarchical and acentered structures in biology [a paper in System's Biology that exposes the function of closure in creating global behaviour]
The Cancer Journal (1989) 2: 285-287

V de Lorenzo, A Danchin
Synthetic biology: discovering new worlds and new words
EMBO Rep (2008) 9: 822-827 pubmed probactys

fr A Danchin
Sélection naturelle et immortalité
in: Les mondes darwiniens (T Heams, P Huneman, G Lecointre, M Silberstein, eds), Syllepse (2009) pp 445-470 biosapiens

Tous les organismes – bactéries incluses – vieillissent et meurent. En raison de l’incroyable diversité de ce processus (les plantes vieillissent lentement, par exemple), c’est un lieu commun des études sur le vieillissement que de considérer qu’il s’agit d’un paradoxe, qui requiert par conséquent une explication en profondeur. Cette observation a suscité une profusion d’études fascinantes (et de discussions enflammées) destinées à mettre au jour la variété des causes et des mécanismes impliqués dans le vieillissement. Dans ce contexte, l’« immortalité » est considérée comme la norme. Pourquoi et comment vieillissons-nous ? Ce n’est pas cette question que je traiterai ici, je vais prendre le chemin exactement opposé. Considérant que le vieillissement est une conséquence directe de la physique – et c’est en effet l’une des conclusions majeures à laquelle parviennent ceux qui analysent le vieillissement en profondeur quand il repensent les théories de l’« avalanche d’erreurs» d’Orgel ou le « cliquet de Muller –, j’observe au contraire que c’est l’immortalité (que nous observons dans le cancer) qui soulève un paradoxe...

A. Danchin
Information of the chassis and information of the program in synthetic cells
Syst Synth Biol (2009) 3(1-4):125-134 pubmed probactys tarpol pdf

A Danchin
Perfect time or perfect crime?
EMBO Reports (2010) 11: 74 pubmed

Opening: Imagine the situation: “[O]ne day, you notice an old country woman crossing a downtown street, just about to put one foot down on the rails of the streetcar line. […] Suppose, now, that at the very moment she puts her foot on the rail a streetcar comes rushing down the tracks toward her. If the old woman does not notice the car and continues across the tracks nothing will happen. But if someone should happen to shout ‘Look out, old woman!’ what would be her natural reaction? […] she would suddenly become flustered and would pause to decide whether to go on or step back […] the mere words ‘Look out, old woman!’ would be as dangerous a weapon as any knife or firearm. […] the man who sounds the warning actually becomes a murderer!" (Ranpo, 1956). In this sense, the Asilomar conference on genetic engineering in 1974 was the perfect crime in using cautionary exclamations asa weapon that had far-reaching consequences for the emerging field of molecular biology: a moratorium stopped research in some places while others proceeded and took the lead. The same fate may lie in store for synthetic biology (SB). The usual crooners have understood the importance of resorting to appeals to ethics and playing on people’s fears to make themselves known and have begun a discussion of the purported dangers of creating organisms a la carte. Such clamouring for attention may yet end up being a shot to our own feet. Moreover, does minimization of a bacterial genome really pose ethical questions? Should we worry, and if so why? After all, what is the purpose of SB? We need to explore the knowledge that we are required to master to (re)construct life in order to gain a better idea of the economic and ethical questions that we have to ask before we start asking them.

A Danchin, G Fang
Babies are born very young. The synthesis of change
Journal of Cosmology (2010) 7: May 2010 Artificial Life


Motifs, words, patterns

C Médigue, A Viari, A Hénaut, A Danchin
Escherichia coli molecular genetic map (1500 kbp): update II
Mol Microbiol (1991) 5: 2629-2640 pubmed

Palindromic motifs are distributed in an unequal fashion in the E. coli genome. In particular some words such as TA, TAG and CTAG are rarer than predicted

 

Nous y étudions la répartition des sites palindromiques, et nous commençons à proposer quelques règles fondées sur l'observation de la non-symétrie des di- et tri- nucléotides

A Hénaut, T Rouxel, A Gleizes, I Moszer, A Danchin
Uneven distribution of GATC motifs in the Escherichia coli chromosome, its plasmids and its phages
J Mol Biol (1996) 257: 574-585 pubmed

This in-depth study shows the necessity to compare sequences to a non-random background, but to a realistic model of the chromosome to permit construction of significant statistics for motif search

 

Cette étude approfondie, dans un cas particulier, insiste sur le fait qu'il faut un modèle réaliste du chromosome pour pouvoir faire une statistique qui soit un peu significative

A Hénaut, A Danchin
Analysis and Predictions from Escherichia coli sequences or E. coli in silico
In: Escherichia coli and Salmonella, Cellular and Molecular Biology (Editor in Chief: Frederick C Neidhardt) vol. 1, chap 114, pp 2047-2065

In the E. coli "Bible", many questions underlying numerology of nucleotides are described in some detail

 

Dans la "Bible" de E. coli, nombre dequestions sous-jacentes à la numérologie des nucléotides sont exposées en détail

A Hénaut, F Lisacek, P Nitschké, I Moszer, A Danchin
Global analysis of genomic texts: the distribution of AGCT tetranucleotides in the Escherichia coli and Bacillus subtilis genomes predicts translational frameshifting and ribosomal hopping in several genes
Electrophoresis (1998) 19: 515-527 pubmed

This thorough analysis develops some remarkable consequences of the comparison of the real chromosome sequence to that of a "realistic" one. As usual, the interesting observations are the ultimate deviations from the law that are rewarding, as they show that something is happening, and therefore point at a particular natural selection process. This work predicts that some messenger RNAs slip in the ribosome, and give rise to variant proteins that may allow the cells to escape pathogenic processes under stressful conditions

 

Ce travail développe des conséquences remarquables de la comparaison chromosome réel - chromosome "réaliste". Comme toujours ce sont les déviations à la loi ultime qui sont fructueuses car elles montrent que quelque chose se passe, et par conséquent pointent vers une pression de sélection biologique. Ce travail prédit que certains ARN messagers glissent dans le ribosome, et donnent naissance à des variants de certaines protéines permettant à la cellule d'échapper à des processus pathogènes en condition de stress

EPC Rocha, A Viari, A Danchin
Oligonucleotide bias in Bacillus subtilis: general trends and taxonomic comparisons
Nucleic Acids Res (1998) 26: 2971-2980 pubmed pdf

This work provides means to compute exactly what is significant and not significant in motif composition of genomes

 

Ce travail donne le moyen de calculer exactement ce qui est significatif et ce qui ne l'est pas dans le dénombrement des motifs dans les génomes

EPC Rocha, A Danchin, A Viari
Analysis of long repeats in bacterial genomes reveals alternative evolutionary mechanisms in Bacillus subtilis and other competent prokaryotes
Mol Biol Evol (1999) 16: 1219-1230 pubmed pdf

EPC Rocha, A Danchin, A Viari
Functional and evolutionary roles of long repeats in prokaryotes
Res Microbiol (1999) 150: 725-733 pubmed

Two articles analysing long non random repeats in Bacillus subtilis

 

Deux travaux sur les longues répétitions non aléatoires

EPC Rocha, A Danchin, A Viari
Translation in Bacillus subtilis: roles and trends of initiation and termination, insights from a genome analysis
Nucleic Acids Res (1999) 27: 3567-3576 pubmed pdf

The beginning and the end of coding sequences (CDSs) induces a significant bias in the gene sequence start and end

 

Le début et la fin des séquences codantes induit un biais significatif dans la composition du début et de la fin des gènes

EPC Rocha, A Danchin, A Viari
Universal replication biases in bacteria
Mol Microbiol (1999) 32: 11-16 pubmed pdf

A universal rule of the composition of genomes with an origin of replication distinguishes the replication leading strand (enriched in G+T) from the lagging strand (enriched in C+A). The bias is so strong that it is often reflected in the amino-acid composition of the proteins, allowing one to predict, just knowing the content in valine as opposed to threonine and isoleucine, from which strand a protein is coded

 

Une règle universelle pour les génomes qui ont une origine de réplication: GT est enrichi dans le brin direct et CA dans le brin complémentaires. Ce biais est si fort que dans certains cas (Chlamydia trachomatis, Borellia burgdorferi...) on peut prédire, rien qu'en connaissant la séquence de la protéine par quel brin elle est codée !

EPC Rocha, A Danchin, A Viari
The DB case: pattern matching evidence is not significant
Mol Microbiol (2000) 37: 216-218 pubmed pdf

Statistical caveat on the significance of motifs: the downstream box is not statitically significant

 

Une petite mise en garde statistique, sur le décompte des motifs: la boîte aval n'est pas statistiquement significative

HKU_Pasteur
EPC Rocha, A Danchin
Ongoing evolution of strand composition in bacterial genomes
Mol Biol Evol (2001) 18: 1789-1799 pubmed pdf

uk-flagPhylogenetic consequences of a gene changing strand

 

fr-flagQuelques conséquences en termes d'évolution (changement de brin)

EPC Rocha, A Danchin, A Viari
Evolutionary role of restriction/modification systems as revealed by comparative genome analysis
Genome Res (2001) 11: 946-958 pubmed pdf

HKU_Pasteur
EPC Rocha, A Danchin
Base composition bias might result from competition for metabolic resources
Trends Genet (2002) 18: 291-294 pubmed pdf
HKU_Pasteur
X Xia, T Wei, Z Xie, A Danchin
Genomic changes in nucleotide and dinucleotide frequencies in Pasteurella multocida cultured under high temperature
Genetics (2002) 161: 1385-1394 pubmed pdf
HKU_Pasteur
Y Wang, EPC Rocha, FCC Leung, A Danchin
Cytosine methylation is not the major factor inducing CpG dinucleotide deficiency in bacterial genomes
J Mol Evol (2004) 58: 692-700

A few remarks on CG-deficiency: besides a role of methylation it is likely that sequence-dependent structural constraints in DNA biases the genome content in particular patterns

 

Quelques remarques sur l'énigme de la déficience en CG : outre le rôle connu de la méthylation des cytosines il est probable que certaines contraintes dans la structure de l'ADN ont une conséquence sur le contenu en motifs particuliers

HKU_Pasteur
E Larsabal, A Danchin
Genomes are covered with ubiquitous 11bp periodic patterns, the "class A flexible patterns"
BMC Bioinformatics (2005) 6: 206 pubmed BMC

An extraordinary universal constraint: it has long been known that genomes are not random nucleotide sequences. In particular they are covered by regions where nucleotides are correlated every third position. This is the consequence of the dense presence of protein coding regions in the genomes. A second correlation has also been uncovered, but it remained totally unexplained until the present work: there is a correlation on the nature of nucleotides every 10-12 nucleotide. We show that this is due to the presence of a dense network of discontinuous motifs, which are "flexible" (in that the conserved nucleotides are not exactly located at the same position in each and every motif but only approximately so). These motifs are likely to be the hallmark of protein-DNA interactions. There are so densely distributed that in some cases, such as the genome of Helicobacter pylori, one nucleotide in four is determined by a conserved flexible motif.

 

Une extraordinaire contrainte universelle, dont nous sommes loin encore de comprendre toutes les conséquences: on sait depuis longtemps que les génomes ne sont pas une suite aléatoire de nucléotides. On y remarque en particulier une corrélation entre les nucléotides toutes les trois positions, ce qui s'explique facilement par la présence des régions codant les protéines. Mais on observe aussi une corrélation, un peu floue entre les nucléotides toutes les 10 à 12 positions. On n'avait jusqu'à présent aucune idée de leur cause. Le travail présenté montre que cette corrélation est due à des motifs discontinus, flexibles (en ce sens que les nucléotides conservés sont en des positions à peu près conservées), et probablement la marque de l'interaction avec des protéines qui se lient avec le chromosome. Ces motifs sont si densément répartis que, dans certains cas, comme celui de Helicobacter pylori, un nucléotide sur 4 dans le génome est déterminé par ces motifs.


HKU_Pasteur
G Pascal, C Médigue, A Danchin
Universal biases in protein composition of model prokaryotes
Proteins (2005) 60: 27-35 pubmed wiley biosapiens

fr-flagLe nuage des points formés des protéines d'un organisme, réparties dans un espace construit sur la composition en acides aminés sépare d'abord selon la charge électrique des acides aminés, opposée à leur caractère hydrophobe. Cela crée une classe homogène bien indentifiée, formée des protéines intégrales de la membrane interne. Un second biais est imposé par le contenu en G+C du génome, et sépare les protéines en fonction du contenu en G+C de la première position des codons correspondants aux acides aminés. Enfin un rôle remarquable des acides aminés aromatiques crée un troisième biais universel. Les protéines "orphelines" sont enrichies en ces derniers, suggérant qu'ils ont un rôle privilégié dans la création de fonctions nouvelles au cours de l'évolution. Nous postulons que la majorité d'entre elles — les gluons — sont impliquées dans la stabilisation de complexes multimériques, et participent ainsi à la définition du "soi" de l'espèce.

 

UKIn the cloud of points of proteins distributed along the axes of their amino acid composition, the electric charge of amino-acids measured against hydrophobicity creates a highly homogeneous cluster, made exclusively of proteins that areintegral inner membrane proteins. A second bias is imposed by the G+C content of the genome, separating protein according to the G+C content of their first codon position. A remarkable role of aromatic amino-acids creates a third universal bias. Expressed orphan proteins are enriched in these residues, suggesting that they might participate in a process of gain of function during evolution. We postulate that the majority is made of proteins — gluons — involved in stabilising complexes, thus defining the "self" of the species.

G Pascal, C Médigue, A Danchin
Persistent biases in the amino-acid composition of prokaryotic proteins
Bioessays (2006) 28: 726-738 pubmed pdf  biosapiens b7

 

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The principles of molecular biology and their formal consequences

fr A Danchin
Règles de réécriture en biologie moléculaire
Change (1974) 19: 10-24

In his inaugural lesson at the Collège de France, François Jacob reflected about possibly analogies between the structure of the written language and that of the genetic programme. A few years later he discussed the topic with the linguist Roman Jacobson. This theme has initiated the experimental work of Antoine Danchin on the role of "secundary punctuation" in the process of tranlation of the genetic message. This is discussed in this text of the journal Change (Seghers), after he had uncovered an unexpected function of secundary punctuation in bacteria
 
Dans sa leçon inaugurale au Collège de France, François Jacob s'interrogeait sur les analogies possibles entre la structure du langage écrit, et le programme génétique. Un peu plus tard il en débattait avec le linguiste Roman Jacobson. Ce thème a été le déclencheur des travaux d'Antoine Danchin sur le rôle de la "ponctuation secondaire" dans le phénomène de traduction du message génétique, et c'est ce qu'il expose dans ce texte de la revue Change (Seghers), après avoir découvert une fonction inattendue de la ponctuation secondaire chez les bactéries

A Danchin
Genome diversity: A grammar of microbial genomes
ComPlexUs (2004/2005) 2: 61-70 turing_machines CPU_Turing biosapiens

G Fang, EPC Rocha, A Danchin
How essential are non-essential genes?
Mol Biol Evol (2005) 22: 2147-2156 pubmed  biosapiens

Gene essentiality has usually been identified in prokaryotes by growth properties under laboratory conditions. This is obviously an extremely biased view of the importance of a gene in real life. We explored the nature of essentiality in Bacteria (a similar work needs to be done in the other kingdoms of life) by looking for "persistent" genes, i;e. genes that not only are kept as orthologs in a wide variety of Bacteria, but also that keep common rules of organisation in the genome, as well as a certain pattern of evolution. This allowed us to measure the real nature of essentiality and to have some insight about the extent of acquisitive evolution whereby different structures are recruited for a given function. This work provides a phylogenetic contribution to the BioSapiens effort by creating a resource for functional gene annotation

 

On identifie habituellement le caractère essentiel d'un gène par les propriétés de croissance d'une bactérie en laboratoire. Cette vue est évidemment extrêmement biaisée et ne rend nullement compte de l'importance d'un gène dans la vie réelle. Nous avons exploré la nature de l'essentialité des gènes chez les Bactéries (un travail analogue sera nécessaire pour les autres règnes) en recherchant le caractère de "persistance" des gènes, c-à-d non seulement leur caractère d'orthologie dans un grand nombre de Bactéries, mais aussi le fait qu'ils conservent un certain nombre de propriétés par rapport à l'organisation du génome et un certain schéma d'évolution. Cela nous a permis de mesurer la nature réelle de l'essentialité et nous a donné quelques idées sur la capture de structures destinées à remplir une même fonction (évolution acquisitive). Ressource pour l'annotation fonctionnelle des gènes (programme BioSapiens)

M Bailly-Bechet, A Danchin, M Iqbal, M Marsili, M Vergassola
Codon usage domains over bacterial chromosomes
PLoS Computational Biology (2006) 2: e37  pubmed codon usage F1000

Addendum (October 18, 2006)
coli_correl ( 20 K)

An issue left unexplained in this paper is the striking quantitative difference between E. coli and B. subtilis. This is clearly visible in Fig. 6, where it is shown the probability that two genes at distance l belong to the same cluster of codon usage. Clusters are characterized by a similar codon bias and were identified using a novel information-based clustering method. While both curves decay on distances sizably longer than what could be accounted by operons, B. subtilis curve manifestly features much longer correlations. It is hard to develop a biologically well-founded explanation for such a striking difference between the two organisms.

More (64 K)....

subtilis_correl (28 K)

uk-flagThe codon usage bias in genomes has long been associated to specific biological processes, and in particular to the horizontal transfer of genes. A finer analysis of the neighborhoods of genes with similar codon biases has uncovered an important functional correlation between neighboring genes. However, until the present work, the exact influence of translation had not been demonstrated. We show that the diffusion of rare or moderately expressed transfer RNAs is reflected in genomes by the formation of islands of common codon usage bias significantly longer than operons (30 kilobases in E. coli and 150 kilobases in B. subtilis) and that the distribution of these islands is correlated with the functions they code for.

 

fr-flagLe biais d'usage des codons dans les génomes a depuis longtemps été associé à des processus biologiques spécifiques, et en particulier au transfert horizontal des gènes. Une analyse plus fine des voisinages d'usage des mêmes codons a montré une importante corrélation fonctionnelle. Mais, jusqu'au travail ici présenté, l'influence exacte de la traduction n'avait pas été mise en évidence. Nous montrons que la diffusion des ARN de transfert rares ou modérément représentés se reflète dans les génomes par la formation d'îlots nettement plus longs que les opérons (30 kilobases chez E. coli et 150 kilobases chez B. subtilis) et que la répartition de ces îlots est corrélée aux fonctions qu'ils codent.

A Danchin
Archives or palimpsests? Bacterial genomes unveil a scenario for the origin of life
Biological Theory (2007) 2: 52-61 b7

fr A Danchin
De la biologie symplectique à la biologie synthétique
In: L'Homme Artificiel (sous la direction de JP Changeux), Odile Jacob, Paris (2007) pp 61-86

A Danchin, G Fang, S Noria
The extant core bacterial proteome is an archive of the origin of life
Proteomics (2007) 7: 875-889 pubmed biosapiens b7 epg

G Fang, EP Rocha, A Danchin
Persistence drives gene clustering in bacterial genomes
BMC Genomics (2008) 9: 4 pubmed BMC biosapiens b7 HA

uk-flagOur work now culminates in the description of the organisation of bacterial genomes as made of two parts. The paleome, made of genes that tend to be clustered together, codes for functions that are reminiscent of a scenario of the origin of life. It codes for processes that are shared by all bacteria which can live an independent life. About one half of these genes cannot be inactivated, and are usually considered essential genes. The second half has the role of permitting perpetuation of life. The second part of the genome, made of a highly variable set of genes, mostly acquired by horizontal transfer of genes, forms the cenome, coding for the functions that are necessary to occupy a particular niche.

paleome_cenome

fr-flagNotre travail culmine à présent dans une description de l'organisation des génomes bactériens en deux parties. Le paléome, fait de gènes qui tendent à rester ensemble, code des fonctions qui rappellent un scénario de l'origine de la vie. Il code des processus partagés par toutes les bactéries qui peuvent vivre de façon autonome. La moitié de ces gènes ne peut pas aêtre inactivée et ils sont généralement considérés comme essentiels. L'autre moitié a pour rôle de perpétuer la vie. La deuxième partide du génome, très variable, est faite de gènes pour l'essentiel acaquis par transfert horizontal. Elle constitue le cénome, qui code les fonctions qui sont nécessaires à la cellule pour occuper une niche particulière.

 

A Danchin
Natural selection and immortality
Biogerontology (2009) 10: 503-516 pubmed  pdf biosapiensprobactys

A Danchin
Bacteria as computers making computers
FEMS Microbiol Rev (2009) 33: 3-26 pubmed pdf biosapiens probactys

A Danchin
Cells need safety valves
Bioessays (2009) 31: 769-773 pubmed probactys tarpol

In Escherichia coli, the role of lacA, the third gene of the lactose operon, has remained an enigma. I suggest that its role is the consequence of the need for cells to have safety valves that protect them from the osmotic effect created by their permeases. Safety valves allow them to cope with the buildup of osmotic pressure under accidental transient conditions. Multidrug resistance (MDR) efflux, thus named because of our anthropocentrism, is ubiquitous. Yet, the formation of simple leaks would result in futile influx/efflux cycles. Versatile modification enzymes with low sensitivity solve the problem if the modified metabolite is the one exported by MDR permeases. This may account for the pervasive presence of acetyltransferases, such as LacA, associated to acetyl-metabolite exporters. This scenario of constraints imposed by efficient influx of metabolites provides us with a model that should be followed when constructing synthetic cells

A Danchin, A Sekowska
Physico-chemical prerequisites for the construction of a synthetic cell
in: Synthetic Chemistry, May 26th - 30th, 2008, in Bozen, Italy
Beilstein Institut for the Advancement of Chemical Sciences (2009) 1-13 probactys

F Fourmentin, A Danchin
A sequel to "Cells need safety valves"
Symplectic Biology (2010) 1: 1

G Postic, A Danchin, U Mechold
Characterization of NrnA homologs from Mycobacterium tuberculosis and Mycoplasma pneumoniae
Symplectic Biology (2010) 1: c390t9c12uxx.1 microme


Metabolic networks

speA, speB, speE: A Sekowska, P Bertin, A Danchin
Characterization of polyamine synthesis pathway in Bacillus subtilis 168
Mol Microbiol (1998) 29: 851-858 pubmed pdf

speB, argI: A Sekowska, A Danchin, JL Risler
Phylogeny of related functions: the case of polyamine biosynthetic enzymes
Microbiology (2000) 146: 1815-1828 pubmed pdf

HKU_Pasteur
A Sekowska, HF Kung, A Danchin
Sulfur metabolism in Escherichia coli and related bacteria: facts and fiction
J Mol Microbiol Biotechnol (2000) 2: 145-177 pubmed pdf

EPC Rocha, A Sekowska, A Danchin
Sulphur islands in the Escherichia coli genome: markers of the cell's architecture?
FEBS Lett (2000) 476: 8-11 pubmed pdf

JY Coppée, S Auger, E Turlin, A Sekowska, JP Le Caer, V Labas, V Vagner, A Danchin, I Martin-Verstraete
Sulfur-limitation-regulated proteins in Bacillus subtilis: a two-dimensional gel electrophoresis study
Microbiology (2001) 147: 1631-1640 pubmed pdf



The methionine salvage pathway

msp

speD: A Sekowska, JY Coppée, JP Le Caer, I Martin-Verstraete, A Danchin
S-adenosylmethionine decarboxylase of Bacillus subtilis is closely related to archaebacterial counterparts
Mol Microbiol (2000) 36: 1135-1147 pubmed pdf

speE: A Sekowska, P Bertin, A Danchin
Characterization of polyamine synthesis pathway in Bacillus subtilis 168
Mol Microbiol (1998) 29: 851-858 pubmed pdf

mtnN: A Sekowska, A Danchin
Identification of yrrU as the methylthioadenosine nucleosidase gene in Bacillus subtilis
DNA Res (1999) 6: 255-264 pubmed

HKU_Pasteur
mtnK: A Sekowska, L Mulard, S Krogh, JK Tse, A Danchin
MtnK, methylthioribose kinase, is a starvation-induced protein in Bacillus subtilis
BMC Microbiol (2001) 1: 15 pubmed BMC
HKU_Pasteur
mtnW, mtnX, mtnD, mtnE: A Sekowska, A Danchin
The methionine salvage pathway in Bacillus subtilis
BMC Microbiol (2002) 2: 8 pubmed BMC HA

Many metabolites are orphan metabolites, in that their becoming has almost never been studied in details. This is the case of methyl-thioadenosine, produced during polyamines synthesis (and production of ethylene in plants). This work in B. subtilis is the first one to use a genetic systematic approach to identify the genes involved in thiomethyl- salvage, in an economical way, without oxidation. It shows that a gene with considerable resemblance to ribulose bisphophate carboxylase oxygenase (RuBisCO, the most abundant enzyme on Earth) is involved in the cycle, and it identifies all the genes that are necessary for the "methionine salvage pathway"

 

Beaucoup de métabolites sont "orphelins" en ce que leur devenir n'a pratiquement pas été étudié. C'est le cas du méthyl-thioadénosine, produit au cours de la synthèse des polyamines (et de l'éthylène chez les plantes). Ce travail chez B. subtilis est le premier a utiliser une approche génétique pour tenter d'identifier les gènes impliqués dans le cycle qui permet la récupération du groupement thiométhyl d'une façon économique, sans oxydation. Il montre en particulier qu'un gène très semblable à la ribulose bisphophate carboxylase oxygénase (RuBisCO, l'enzyme la plus abondante de la planète) est impliquée dans le cycle, et il identifie tous les gènes nécessaire au recyclage

mtnW: H Ashida, A Danchin, A Yokota
Was photosynthetic RuBisCO recruited by acquisitive evolution from RuBisCO-like proteins involved in sulfur metabolism?
Res Microbiol (2005) 156: 611-618 pubmed pdf

HKU_Pasteur
mtnA, mtnB, mtnC, mtnP: A Sekowska, V Dénervaud, H Ashida, K Michoud, D Haas, A Yokota, A Danchin
Bacterial variations on the methionine salvage pathway
BMC Microbiol (2004) 4: 9 pubmed BMC biosapiens

mtnW: H Ashida, Y Saito, T Nakano, N Tandeau de Marsac, A Sekowska, A Danchin, A Yokota
RuBisCO-like proteins as the enolase enzyme in the methionine salvage pathway: functional and evolutionary relationships between RuBisCO-like proteins and photosynthetic RuBisCO
J Exp Bot (2008) 59: 1543-1554
pubmed

HKU_Pasteur
mtnW: Y Saito, H Ashida, T Sakiyama, N Tandeau de Marsac, A Danchin, A Sekowska, A Yokota
Structural and functional similarities between a RuBisCO-like protein from Bacillus subtilis and photosynthetic RuBisCO
J Biol Chem (2009) [Epub ahead of print] pubmed pAp

mtnU: E Belda E, A Sekowska, F Le Fèvre, A Morgat, D Mornico, C Ouzounis, D Vallenet, C Médigue, A Danchin
An updated metabolic view of the Bacillus subtilis 168 genome
Microbiology (2013) 159: 757-770. doi: 10.1099/mic.0.064691-0 pubmed

 

HKU_Pasteur
mapA, mapB: CH You, HY Lu, A Sekowska, G Fang, YP Wang, AM Gilles, A Danchin
The two authentic methionine aminopeptidase genes are differentially expressed in Bacillus subtilis
BMC Microbiology (2005) 5: 57 pubmed BMC HA

A Danchin
A path from predation to mutualism
Molecular Microbiology (2010) 77: 1346-1350 pubmed


ascR, snaA, tcyJ, tcyK, tcyL, tcyM, tcyN, cmoO, cmoI, cmoJ, rbfK, sndA, ytnM : CM Chan, A Danchin, P Marlière, A Sekowska
Paralogous metabolism: S-alkyl-cysteine degradation in Bacillus subtilis
Environ Microbiol (2014) 16: 101-117 pubmed

A Danchin, A Sekowska
The logic of metabolism and its fuzzy consequences
Environ Microbiol (2014) 16: 19-28 pubmed

The cell chassis

PM Binder, A Danchin
Life's demons: information and order in biology. What subcellular machines gather and process the information necessary to sustain life?
EMBO Reports (2011) 12: 495-499 PubMed

In his seventeenth-century classic, Novum Organum, Francis Bacon wrote, “we cannot command nature except by obeying her” (Bacon, 2010). Although our knowledge of living systems is much improved since Bacon’s time, we are still far from understanding—or commanding—all the complex mechanisms of life. To take full advantage of living organisms for the benefit of mankind, we will need to understand those mechanisms to the furthest possible extent. To do so will require that the concept of information and the theories of information science take a more-prominent role in the understanding of living systems...

A Danchin
Les gènes du démon de Maxwell : est-il possible de construire une usine cellulaire ?
Maxwell’s demon’s genes: Can we build a cell factory?
Comptes Rendus de l'Académie des Sciences, Chimie (2011) 14: 413-419 microme

A Danchin, A Sekowska
The role of information in evolutionary genomics of bacteria
In: Evolutionary genomics and systems biology (G Caetano-Anollés, Editor), Wiley & sons, Hoboken, NJ (2010) pp 81-94
biosapiens probactys
  evolution

A Danchin, PM Binder, S Noria
Antifragility and tinkering in biology (and in business): Flexibility provides an efficient epigenetic way to manage risk
Genes (2011), 2: 998-1016; doi:10.3390/genes2040998 microme

M Porcar, A Danchin, V de Lorenzo, VA dos Santos, N Krasnogor, S Rasmussen, A Moya
The ten grand challenges of synthetic life
Systems and Synthetic Biology (2011) 5: 1-9 PubMed microme

A Danchin
Scaling up synthetic biology: Do not forget the chassis
FEBS Letters (2012)586: 2129-2137. PubMed microme

A Danchin
Synthetic biology's flywheel
EMBO Reports (2012) 13: 92 PubMed


MF Liu, S Cescau, U Mechold, J Wang, D Cohen, A Danchin, HJ Boulouis, F Biville
Identification of a new nanoRNase in Bartonella
Microbiology (2012)158: 886-895 pubmedtarpol

G Postic, A Danchin, U Mechold
Characterization of NrnA homologs from Mycobacterium tuberculosis and Mycoplasma pneumoniae
RNA (2012) 18: 155-165 PubMed microme

italiaA Danchin
I geni del diavoletto di Maxwell
Prometeo (2012) 117: 120-125


CG Acevedo-Rocha, G Fang, M Schmidt, DW Ussery, A Danchin
From essential to persistent genes: a functional approach to constructing synthetic life
Trends Genet. (2013) 29: 273-279. doi: 10.1016/j.tig.2012.11.001 pubmed

V de Lorenzo, A Sekowska, A Danchin,
Chemical reactivity drives spatiotemporal organisation of bacterial metabolism
FEMS Microbiology Reviews (2015) 39: 96-119
Abstract We examine how bacterial metabolism is shaped by chemical constraints acting on the material and dynamic layout of enzymatic networks and beyond. These are moulded not only for optimisation of given metabolic objectives (e.g. synthesis of a particular amino acid or nucleotide) but also for curbing the detrimental reactivity of chemical intermediates. Besides substrate channelling, toxicity is avoided by barriers to free diffusion (i.e. compartments) that separate otherwise incompatible reactions, along with ways for distinguishing damaging vs. harmless molecules. On the other hand, enzymes age and their operating lifetime must be tuned to upstream and downstream reactions. This time dependence of metabolic pathways creates time-linked information, learning and memory. These features suggest that the physical structure of existing biosystems, from operon assemblies to multicellular development may ultimately stem from the need to restrain chemical damage and limit the waste inherent to basic metabolic functions. This provides a new twist of our comprehension of fundamental biological processes in live systems as well as practical take-home lessons for the forward DNA-based engineering of novel biological objects
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Dernière mise à jour 9 décembre 2015

Last update december 9th 2015