The i-Bio program awarded 4 PhD fellowships in 2021.

Interface Biology and Chemistry

Meeting with Mazarine Desplanque

My scientific background
As a student of the pharmacy-science program of the “Ecole de l’Inserm”, I have been aspiring for years to become a pharmacist as well as a researcher. Early I had the opportunity to work with chemists, biologists, pharmacists and physicians and these experiences convinced me of the importance of preserving a transversal thinking between fundamental science and medical knowledge. Therefore, I felt it was essential to undertake a PhD thesis in order to effectively work towards this endeavor of mine.

What attracts me to the PhD experience
I am truly looking forward to achieving a PhD experience as my different internships gave me the desire to conduct my own experiments and assume a greater role in science. I am also enthusiastic about exchanging with the two laboratories. Furthermore, undertaking a PhD at this stage of my studies, before my pharmacy externship, will then allow me to finish my pharmaceutical studies with a new vision.

My future research
The striatum plays a central role in the regulation of reward and habits-guided behaviors as well in locomotor activity. Striatal activity is regulated by cholinergic interneurons (CINs) that display unique molecular characteristics: they express vesicular transporter for acetylcholine (VAChT) and for glutamate (VGLUT) and consequently regulate the striatal network with both ACh and Glu. However, the specific morphological and functional characteristics of ACh/Glu co-transmission are still poorly understood. Our hypothesis is that CINs contain three pools of synaptic vesicles expressing either VAChT, VGLUT3 or both releasing ACh, Glu or both. To explore this hypothesis, we will use a multidisciplinary approach combining super resolution microscopy, new chemical tools (fluorescent sensors to locate VGLUT) and optogenetic stimulations. This project will lead to a deeply understanding of the striatum and could open the way to new treatments for addiction or Parkinson disease. It will not only bring knowledge progress, it will also contribute to the development of pivotal tools such as fluorescent VGLUT ligands, bridging neurosciences and pharmacological research.

Figure

Striatal sections were treated for the immunohistochemical detection of VAChT and VGLUT3. A cholinergic varicosity was observed by confocal microscopy and by super resolution STED microscopy. In contrast to confocal microscopy, STED shows that VAChT- and VGLUT3 immunopositive fluorescent puncta are largely non-overlapping.

Find out more:
[1] El Mestikawy, Salah et al. “From glutamate co-release to vesicular synergy: vesicular glutamate transporters.” Nature reviews. Neuroscience vol. 12,4 (2011): 204-16. doi:10.1038/nrn2969
[2] Gubernator, N. G. et al. Fluorescent false neurotransmitters visualize dopamine release from individual presynaptic terminals. Science 324, 1441-1444, doi:10.1126/science.1172278 (2009).
[3] S Ren, J. et al. Habenula “Cholinergic” Neurons Corelease Glutamate and Acetylcholine and Activate Postsynaptic Neurons via Distinct Transmission Modes. Neuron 69, 445-452 (2011), doi:10.1016/j.neuron.2010.12.038

Contact
Mazarine DESPLANQUE
Email: mazarinedesplanque1999@gmail.com

  1. Team “Neuropharmacology of VGLUTs”
    Neurosciences Paris Seine (NPS) – CNRS UMR 8246 – INSERM U1130- Sorbonne Université
    Institut Biologie Paris-Seine
    7-9 quai Saint Bernard – Bât B 4ème étage
    75 252 Paris CEDEX, France
    https://www.ibps.sorbonne-universite.fr/fr/Recherche/umr-8246/systemes-glutamatergiques-normaux-et-pathologiques
  2. Team “Biomolecules: Analysis, Molecular and Cellular Interactions”
    Laboratoire des BioMolécules (LBM), UMR 7203, CNRS – ENS – Sorbonne Université
    4 place Jussieu – Tour 23-33
    Paris 75005, France
    https://lbm.cnrs.fr/

Interface Biology and Physics/Engineering

Meeting with Giorgia Marcelli

My scientific background
I have always been fascinated by physical sciences and mathematical formalisms. During my under-graduated studies, I learned how the description of Complex Systems deeply affects the way we understand our surrounding reality. In my Master thesis, I had the opportunity to apply abstract concepts into a Biological Physics project, with the goal of describing cell-driven micro-transport of a bio-hybrid system. All the people I met during this experience inspired me a lot to do research.

What attracts me to the PhD experience
What attracts me most about pursuing a PhD is the possibility to broaden my knowledge and keep learning. I like the idea of exchanging notions and the possibility of building up a scientific environment that can change my way of thinking. During the following path I wish to contribute fully in the understanding of the biological processes that lead cell-cell communication.

My future research
Cells communicate with each other by exchanging chemical and physical information. This process contributes to regulate and synchronize correctly all cellular functions. My PhD project aims at understanding the transport mechanism across a given junction, i.e. a well-defined channel of proteins that connects two cells.

To do so, we will mimic an animal tissue via a biomimetic approach, using a 2D network of Droplet Interface Bilayers (DIBs). Direct communication between cell-like compartments will be obtained by decorating DIBs with two types of transmembrane proteins, -Hemolysin and mechanosensitive channel for large conductance (MscL).

In both cases, the diffusivity of  ions will be probed. Using MscL proteins will allow us to investigate mechanosensitive networks. By applying an external mechanical stress on the DIBs we will study how such perturbations influence the transport properties. Moreover, the role of tissue topology in transport laws will also be inquired, with the aim of fully describing the process both from a microscopic and mesoscopic point of view.

Figure

Drawing of the 2D DIB network: aqueous droplets are printed in a bath of oil by microfluid techniques. A lipid bilayer forms at the contacting interface of two adjacent droplets. In green, the diffusivity of  ions is highlighted – this will be probed by mean of epifluorescence imaging.

Find out more
[1] Diffusion through nanopores in connected lipid bilayer networks, M. Valet et al., Physics Review Letter, (2019), https://doi.org/10.1103/PhysRevLett.123.088101.
[2] Quasistatic Microdroplet Production in a Capillary Trap, M. Valet et al., Physics Review Applied 9, (2018), https://doi.org/10.1103/PhysRevApplied.9.014002.
[3] Activation of bacterial channel MscL in mechanically stimulated droplet interface bilayers, J. Nayem et al., Sci Rep 5, 13726 (2015), https://doi.org/10.1038/srep13726.

Contact
Giorgia Marcelli
Email: marcelli.giorgia@gmail.com

  1. Jean Perrin Laboratoire (LJP)CNRS UMR 8237, Sorbonne Université
    Institut de Biologie Paris-Seine
    4, place Jussieu, Tour 32-33, Case 114
    75005 Paris, France
    http://www.labos.upmc.fr/ljp/
  2. Noireaux Lab, University of Minnesota
    Physics and Nanotechnology
    115 Union street se
    Minneapolis, MN 55455, USA
    https://www.noireauxlab.org/index.html

Interface Biology and Maths/Modeling/Computer science

Meeting with Konstantin Volzhenin

My scientific background
I have a general background in Physics and Mathematics, however, during my Master studies, I became interested in Artificial Intelligence and its applications in Biology in particular. I have worked in both industrial and academic research, applying my knowledge to different topics, such as Neuroscience or Robotics. My current project in Metagenomics tackles very interesting and exciting questions in a field that can greatly benefit from new AI tools.

What attracts me to the PhD experience
I think that PhD research provides unique opportunities to set a creative atmosphere. This allows implementing of various interesting ideas and finding nontrivial solutions. Moreover, I find it very exciting to work on unusual and difficult problems on a regular basis and I believe that academic research is a perfect place for this.

My future research
My work will be dedicated to developing a new computational approach to reconstruct protein-protein interaction (PPI) networks for metagenomic samples. I will create a Deep Learning model that will have to deal with a specific classification task: it will predict which proteins from a specific microbial community can interact with each other and it will estimate the likelihood of such interactions. This work has never been done before for a group of organisms thus it can serve as an important tool to study Ecosystems Biology on the smallest, molecular scale. I am very excited by the interdisciplinary nature of this project which combines state-of-the-art AI research with large-scale biological datasets in order to shed some light on incredibly complex interactions in the living world.

Figure

Find out more
[1] Vicedomini R, Bouly JP, Laine E, Falciatore A, Carbone A. Multiple probabilistic models extract features from protein sequence data and resolve functional diversity of very different protein families. bioRxiv. 2021 Jan 1;717249. https://www.biorxiv.org/content/10.1101/717249v2
[2] Ugarte A, Vicedomini R, Bernardes J, Carbone A. A multi-source domain annotation pipeline for quantitative metagenomic and metatranscriptomic functional profiling. Microbiome. 2018 Aug 28;6(1):149. https://doi.org/10.1186/s40168-018-0532-2

Contact
Konstantin VOLZHENIN
Email: Konstantin_v_v@outlook.com

  1. Team “Analytical Genomics”
    Laboratory of Computational and Quantitative Biology (LCQB) UMR 7238 CNRS – Sorbonne University
    Institut de Biologie Paris-Seine
    7-9 Quai Saint Bernard, Bâtiment C, 4ème étage
    75005 Paris, France
    https://www.ibps.sorbonne-universite.fr/en/research/computational-and-quantitative-biology/analatical-genomics
  2. Team “Atelier de bio-informatique“
    Institut de Systématique, Evolution, Biodiversité (SYEB) UMR 7205 CNRS – EPHE – Sorbonne University
    Muséum National d’Histoire Naturelle
    45 rue Buffon, Bâtiment d’Entomologie
    75005 Paris, France
    https://isyeb.mnhn.fr/fr/atelier-de-bio-informatique-384

Interface Biology and Maths/Modeling/Computer science

Meeting with Zoheir Ziriat

My scientific background
I have always been interested in epigenetic mechanisms and all the fascinating and incredible ways they allow the regulation of gene expression. During my Master on Biochemistry and Genetics of RNA at Sorbonne University and internships, I’ve met many researchers and PhD students working on these topics, all with very different techniques and approaches. These meetings confirmed my interest in the study of epigenetic and motivated me to do a PhD in order to deepen our understanding of this research field.

What attracts me to the PhD experience
For me, a PhD is like diving into a maze and trying, using different techniques and exploring different directions, to find our way to its center and the scientific truth that lies within. I am very excited to undertake this long-term exploration of a subject that fascinates me, and looking forward to learning new techniques, analyzing my results, interacting with others and managing this project.

My future research
At the beginning, there were Transposable Elements (TEs). These are DNA sequences capable of moving and inserting themselves elsewhere in a genome. They represent a huge part of eukaryotic genomes, and thus, could be deleterious. To control TEs, evolution has developed a mechanism based on small non-coding RNAs called piRNAs. These are transcribed from heterochromatic loci composed of fragments of TEs: the piRNA clusters, and we know very little about these genomic regions.

My PhD project aims to decipher the mechanisms behind the evolution and the regulation of piRNA clusters in order to understand how these loci react to the insertion of a new TE and how their transcripts are recognized as piRNA precursors. To do so, I will be using Nanopore 3rd generation sequencer to study piRNA clusters transcripts, and different types of informatics algorithms to try to detect potential chemical RNA modifications in their sequence that could act as tags.

Figure

Nanopore flowcells are composed of pores like this (upper panel, blue) through which an ionic current passes. When an RNA molecule passes through the pore, each nucleotide disturbs this current and generates an electrical signal specific to it (lower panel). When a modified base passes through the pore, a deviation of the signal (orange), specific to the modification in question, is observed.

Find out more
[1] Czech, Benjamin, et Gregory J. Hannon. « One Loop to Rule Them All: The Ping-Pong Cycle and PiRNA-Guided Silencing ». Trends in Biochemical Sciences 41, no 4 (2016): 324-37. https://doi.org/10.1016/j.tibs.2015.12.008
[2] Liu, Huanle, Oguzhan Begik, Morghan C. Lucas, Jose Miguel Ramirez, Christopher E. Mason, David Wiener, Schraga Schwartz, John S. Mattick, Martin A. Smith, et Eva Maria Novoa. « Accurate Detection of m 6 A RNA Modifications in Native RNA Sequences ». Nature Communications 10, no 1 (2019): 4079. https://doi.org/10.1038/s41467-019-11713-9

Contact
Zoheir ZIRIAT
Email: zoheir.ziriat@sorbonne-universite.fr

  1. Team “TErBio: Transgenerational epigenetics & small RNA biology”
    Developmental Biology Laboratory (LBD) UMR 7622, CNRS, Sorbonne University
    Institut de Biologie Paris-Seine
    9 quai Saint Bernard, case courrier 24
    75 252 PARIS CEDEX, France
    https://www.ibps.sorbonne-universite.fr/en/research/developmental-biology-laboratory/transgenerational-epigenetics-small-rna-biology
  2. ARTbio bioinformatics analyses platform, FR3631 CNRS – Sorbonne University
    Institut de Biologie Paris-Seine
    9 quai Saint Bernard
    75 252 PARIS CEDEX, France
    https://www.artbio.fr/