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Ph.D de

Ph.D
Group : Bioinformatics

Conception, modélisation et simulation in silico d’un nanosystème biologique artificiel pour le diagnostic médical

Starts on 01/10/2013
Advisor : AMAR, Patrick

Funding : Contrat doctoral uniquement recherche
Affiliation : Université Paris-Sud
Laboratory : LRI BIOINFO

Defended on 29/09/2016, committee :
Co-directeurs de thèse
-M. Patrick Amar Maître de Conférences HDR, Université Paris Sud
-M. Franck Molina DR CNRS, CNRS Sys2Diag, Montpellier

Rapporteurs
-M. Gilles Bernot Professeur, Université Nice Sophia Antipolis
-M. Jean-Pierre Mazat Professeur, Université de Bordeaux

Examinateurs
-M. Philippe Dague Professeur, Université Paris Sud
-M. Victor Norris Professeur, Université de Rouen

Research activities :

Abstract :
The medical diagnosis is traditionally done by examining the clinical symptoms
and by searching in samples (blood, urine, biopsies, etc.) for the simultaneous presence (or
absence) of biomarkers of the various pathologies considered by the doctor. The search for
biomarkers is conducted using large equipments in a specialised laboratory; The results being
communicated to the doctor, who will then interpret them by applying a medical diagnosis
algorithm.
We wanted to combine in a single device, for a given disease, the detection of its biomarkers
and an implementation of the appropriate diagnosis algorithm. The presence or absence of a
biomarker can be represented by a boolean variable, and the diagnosis algorithm by a complex
boolean function whose value indicates the presence of the targeted disease.
Our diagnosis device is an articial biochemical nano-computer where logical information is
represented by metabolites and the computations are performed by a synthetic enzymatic network.
To build this computer, it has been necessary to establish a theoretical basis of enzymatic
logical networks. We then used this theory to dene what an enzymatic logic network is, and
how it computes correctly the associated boolean function.
For modularity and reusability reasons, we decided to design libraries of enzymatic logic gates
that implement basic boolean operators, and then to assemble these building blocks to get
the complete logic enzymatic network. So, I have designed and developed two software tools,
NetGate and NetBuild, which will automatically perform these operations.
NetGate creates libraries containing hundreds of enzymatic logic gates obtained from the metabolic
networks of living organisms. Before that, it was necessary to manually analyse these
metabolic networks in order to extract each logic gate.
NetBuild uses a library of logic gates (for example created using NetGate) and assembles them
to build circuits that compute a given boolean function. These circuits use specic metabolites
for its inputs (for example the biomarkers of a pathology) and produce a readily detectable
molecular species (using colorimetry for example).

Ph.D. dissertations & Faculty habilitations
APPRENTISSAGE ET OPTIMISATION SUR LES GRAPHES


ANALYSE DE DONNéES MULTI-MODALES POUR LES PATHOLOGIES COMPLEXES PAR LA CONCEPTION ET L’IMPLéMENTATION DE PROTOCOLES REPRODUCTIBLES ET RéUTILISABLES


DESIGNING INTERACTIVE TOOLS FOR CREATORS AND CREATIVE WORK
Creative work has been at the core of research in Human-Computer Interaction (HCI). I describe the results of a series of studies that look at how creators work, where creators include artists with years of professional practice, as well as learners, or novices and casual makers. My research focuses on three creation activities: drawing, physical modeling, and music composition. For these activities, I examine how artists switch between representations and how these representations evolve throughout their creative process, from early sketches to fine-grained forms or structured vocabularies. I present interactive systems that enrich their workflow (i) by extending their computer tools with physical user interfaces, or (ii) by making physical materials interactive. I also argue that sketch-based representations can allow for user interfaces that are more personal and less rigid. My presentation will reflect on lessons and limitations of this work and discuss challenges for future design-support tools.