ECOLE DOCTORALE SVS

N°154

Fictitious Research Projects

(Available on the website of the Doctoral School as from Friday, June 24 2022)

To give equal opportunity to all candidates irrespective of their home university, candidates will present a "fictitious"
research project, independent of the actual thesis subjects proposed by the Doctoral School. Each project is
accompanied by bibliographical references that serve as a framework for the project.

The candidate is not required to prove to be a specialist of the proposed project but, given his / her research training, to
demonstrate his or her ability to think and to be autonomous. The candidate should elaborate on this project an
introduction, the methods to be implemented, the expected results and their interest. The project should be feasible in
three years. This should not be an article analysis nor a review of the literature. Nor should it be a major laboratory
project.

Each candidate can freely choose from the list of proposed "fictitious" projects the one he wishes to present, whatever
the real thesis topic he is interested in.

The classification of proposed themes is purely indicative, the candidate can take any subject whatever the category
indicated.

The duration of the presentation of the project is of the order of 10 min (the total oral presentation curriculum + project
must not exceed 15 min).

Note: All the referenced articles can be downloaded from the doctoral school website
https://ed-svs.u-bordeaux.fr/Doctorat/Integrer-l-dole-doctorale (heading: Les sujets fictifs)

1. Biochemistry

A. Structural biochemistry

Revue:
Thiery S and Kaimer C (2020) The Predation Strategy of Myxococcus xanthus.Front. Microbiol. 11:2.
doi: 10.3389/fmicb.2020.00002
Article:
Seef, et al. A Tad-like apparatus is required for contact-dependent prey killing in predatory social bacteria. eLife
2021;10:e72409. doi :10.7554/eLife.72409

Predatory bacteria are present in different phyla and apply different mechanisms to kill bacteria of other species
and consume their biomass. These mechanisms remain poorly understood and the review provided sets the
framework for the original strategy used by Myxococcus Xanthus.
You will propose a research project, to be carried out in 3 years, aiming at a better understanding of the predation
mechanism of M. Xanthus based on the results of the article provided highlighting the role of the Kil complex (Tad-
like apparatus). You could, for example, develop structural studies on the Kil complex to better understand either
its function or its assembly, or search for other molecular players involved in the prey lysis mechanism.

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 B. Cellular and metabolic biochemistry

Montes de Oca Balderas P. Mitochondria-plasma membrane interactions and communication. J Biol Chem. 2021
Oct;297(4):101164. doi: 10.1016/j.jbc.2021.101164. Epub 2021 Sep 3. PMID: 34481840; PMCID: PMC8503596.

Mitochondria localization in contact with plasma membrane has been shown in many studies. The underlying
mechanisms of these localization, and its possible physiological (or pathological) functions remain poorly
elucidated, and are treated in the accompanying review.
You will propose a research project, feasable in 3 years on the model of your choice (yeast, animal cells,...) with
the aim to understand better the mechanisms and/or the functions of this localization. For example, you could be
interested in:
- the identification of molecular players of this localization and of its dynamics
and/or
- the relationships between this localization and metabolic regulation, cellular responses to stress, or pathologies
related to mitochondria,
and/or
- the relationships betewwen this localiztion of the transfer of mitochondria between cells.
This is a non-exchaustive list. The subject is largely open on purpose.

2. Cell biology

A. Cell biology & Cancer

Provided reviews:
Review#1: Shireen Attaran, Mina J Bissell. The role of tumor microenvironment and exosomes in dormancy and
relapse. Semin Cancer Biol. 2022 Jan;78:35-44. doi: 10.1016/j.semcancer.2021.09.008.

Review#2: McCoy-Simandle K, Hanna SJ, Cox D. Exosomes and nanotubes: Control of immune cell
communication. Int J Biochem Cell Biol. 2016 Feb;71:44-54. doi: 10.1016/j.biocel.2015.12.006. 15.

Review#3: Di Daniele A, Antonucci Y, Campello S. Migrasomes, new vescicles as Hansel and Gretel white
pebbles? Biol Direct. 2022 Apr 28;17(1):8. doi: 10.1186/s13062-022-00321-1.

Long-distance cell-cell signalling has received considerable attention in the recent years. In this context, many
tumor-derived plasma membrane structures (such as extracellular vesicles, migrasomes, nanotubes…) support
communication between the tumor cells and the microenvironment and therefore play key role in the progression
of cancers.

Using the provided reviews as a background, you will propose a 3-years PhD research project to study the role
of one type of structures involved in tumor/microenvironment communication (at the molecular, cellular and/or
organism level) in a specific tumor-related mechanism of your choice (not restricted to dormancy, which was an
example with the provided review).

The project should include various experimental strategies (in vitro and/or in vivo), leading to improve the basic
knowledge on this topic and/or to propose an innovative therapeutic approach.

3. Genetics

Molecular Mechanisms Driving mRNA Degradation by m6A Modification

Yujin Lee Junho Choe Ok Hyun Park Yoon Ki Kim https://doi.org/10.1016/j.tig.2019.12.007

Adenosine methylation in mRNA, resulting in N6-Methyladenosine (m6A), emerged in recent years as the most
frequent modification of mRNA in Eukaryotic cells. This modification is involved in regulation of gene expression
particularly through the regulation of mRNA stability / degradation. The mechanisms generating m6A modification
and ensuing mRNA degradation are now fairly understood as described in the accompanying review by Lee et al.
However several questions remain to be elucidated (see “Outstanding Questions” box), particularly: 1) are there
unknown proteins or complexes involved in recruiting RNA-degrading enzymes to mRNA in response to m6A
modification?; 2) Are certain m6A modifications and functions specific of particular cell types, tissus or organisms?
And what factors determine such specificity?
In your model system of choice, propose a three year project, using a genetic approach, aimed to address either
question 1) or 2) mentioned above.
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4. Imaging

Simultaneous MR imaging for tissue engineering in a rat model of stroke

Francesca J. Nicholls, Wen Ling, Giuseppe Ferrauto, Silvio Aime & Michel Modo
Scientific Reports | 5:14597 | DOI: 10.1038/srep14597

Characterization of brain‑wide somatosensory BOLD fMRI in mice under dexmedetomidine/isoflurane and

ketamine/xylazine
Taeyi You, Geun Ho Im & Seong‑Gi Kim
Scientific Reports | (2021) 11:13110 | https://doi.org/10.1038/s41598-021-92582-5

Regenerative Medicine is a vast field that develops a variety of therapeutic approaches to restore tissue function.
Tissue Engineering is a sub-field of Regenerative Medicine that designs implants to replace defective or absent
tissues/organs. Some tissue-engineered constructs will combine a scaffold of biomaterial with cells cultured in
vitro to provide both mechanical and biological function. Once this tissue is implanted, it is imperative to
understand what happens to the implanted cells. Will they survive? Will they stay in the implants? Will they
multiply? Will they change?

A variety of methods have been developed to follow implanted cells non-invasively. Magnetic Resonance Imaging
(MRI) is one very effective way to perform this “cell tracking” and to evaluate the behavior of the implants over
time. Nevertheless, these methods solely gives the location of the cells of interest but do not provide information
on their function. Functional MRI is extensively used in humans in order to evaluate the function of neurons during
a task, but rarely in small-animals due to a lack of signal-to-noise ratio and the issue of anesthesia that is
necessary for small-animal imaging.

The student will propose a 3-year study to investigate 1) the faith a engineered-tissue facilitating neuronal
development after its implantation in the rat, and 2) the recovery of brain function after a pathology, like brain
ischemia or brain tumor resection.

5. Immunology

Navigating CAR-T cells through the solid-tumour microenvironment

Andrew J Hou, Laurence C Chen, Yvonne Y Chen
DOI: 10.1038/s41573-021-00189-2 https://pubmed.ncbi.nlm.nih.gov/33972771/

How to improve CAR-T cells to treat solid tumors:

CAR-T cells are a breakthrough immunotherapy. However, thus far, they are only used to target hematopoietic
malignancies. Several roadblocks exist to use CAR-T cells for solid tumors, notably impaired recruitment,
specificity and toxicity. With the help of the provided review articles, the project intends to design a “super”-CAR-
T able to target a solid tumor of your choice, in a durable manner, with a minimal effect on healthy tissues. This
can be administered in a combination therapy to boost efficacy. The project should be feasible in three years and
should present proof-of -principle experiments in an in vitro system and in vivo pre-clinical models.

6. Microbiology

A. Bactériologie

The pan-immune system of bacteria: antiviral defence as a community resource

Bernheim and Sorek. 2020, Nature Review Microbiology.

Bacteria and the viruses that infect them, known as phages, are engaged in a constant arms race. Bacteria
continually evolve new mechanisms of resistance against viruses, while phages evolve countermeasures to
overcome these defence mechanisms. Understanding the dynamics of the interactions between bacteria and
phages has tremendous implications for phage-based therapies, microbial ecology and evolution, as well as the
development of new biotechnological tools (i.e CRISPR). Based on the article below, could you please develop a
research project that will explore in the bacterium of your choice:
1) how one or more predicted defense systems (i.e Restriction Modification, Retrons, Toxin-Antitoxin, CRISPR,
…etc) function as anti-phage defense?
2) how these systems cooperate to defeat bacteriophages?

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 B. Parasitologie

Trypanosome Signaling-Quorum Sensing.

Matthews KR. Annu Rev Microbiol. 2021 Oct 8;75:495-514. doi: 10.1146/annurev-micro-020321-115246. PMID:
34348028.

Trypanosome quorum sensing (QS): characterization of oligopeptide signals and its use for therapeutic
benefit
African trypanosomes are single-celled protozoan parasites that live an extracellular lifestyle both in their
mammalian host and in their tsetse fly vector. The phenomenon of QS in trypanosomes has long been recognized,
but only recently has it been understood in molecular detail. This understanding has provided tools for dissecting
the process in detail and its impact on the biology and pathology of the parasite.

Based on the proposed review, the candidate should build a three years PhD project aiming (i) to explore the
exact specificity of oligopeptide signals and their contribution to trypanosome quorum sensing and (ii) how this
can be exploited for therapeutic advantage.

C. Virologie

Influenza A Viruses: Understanding Human Host Determinants

Ciminski et al. 2021, Trends in Molecular Medicine 104 https://doi.org/10.1016/j.molmed.2020.09.014
Host and viral determinants of influenza A virus species specificity
Long et al. 2019, Nature Reviews in Microbiology https://doi.org/10.1038/s41579-018-0115-z

The past two years have shown that viral zoonosis between humans and animals is a major health threat.
Anticipating what allows a virus to cross the species barrier is key to understand the danger coming from such an
event. In this context please develop a research topic investigating the zoonotic potential of influenza virus by
addressing a select molecular mechanism (e.g. entry, replication, immunity…).

7. Neurosciences

A. Topic 1: Approches cellulaires

Putting the axonal periodic scaffold in order

Christophe Leterrier - https://doi.org/10.1016/j.conb.2020.12.015
CurrentOpinioninNeurobiology2021,69:33–40 This review comes from a themed issue on Molecular Neuroscience

Neurons rely on a unique organization of their cytoskeleton to build, maintain and transform their extraordinarily
intricate shapes. After decades of research on the neuronal cytoskeleton, it is exciting that novel assemblies are
still discovered thanks to progress in cellular imaging methods. Indeed, super-resolution microscopy has revealed
that axons are lined with a periodic scaffold of actin rings, spaced every 190 nm by spectrins. Determining the
architecture, composition, dynamics, and functions of this membrane-associated periodic scaffold is a current
conceptual and technical challenge…” Leterrier, Current Opinion in Neurobiology 2021.

Inspired by the review of Leterrier, Current Opinion in Neurobiology 2021, you will elaborate a three-year PhD
project to dissect the molecular organization or the role of the membrane-associated periodic scaffold (MPS) on
neuronal cell biology and physiology. The scientific question of your project can go from the regulation of
intracellular transport, intrinsic excitability, cell signaling, to the role of MPS un interaction with glial cells... You
are free to propose any experimental approaches to test your hypothesis

B. Topic 2: Approches circuits locaux

Dynamic interplay between GABAergic networks and developing neurons in the adult hippocampus
Mariela F. Trinchero, Damiana Giacomini and Alejandro F. Schinder
Current Opinion in Neurobiology 2021, 69:124–130 This review comes from a themed issue on Molecular
Neuroscience https://doi.org/10.1016/j.conb.2021.03.008

Inspired by the review of Trinchero et al., 2021 you will elaborate a three-year PhD project to dissect the role of
GABAergic interneurons dynamic interplay in the brain function of your choice. You will focus on a local circuit
where the role of GABAergic populations are not fully understood, to identify a clear scientific question. You are
free to propose any experimental approaches to test your hypothesis.

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 C. Topic 3: System neurosciences

A cell type–specific cortico-subcortical brain circuit for investigatory and novelty seeking behavior.
Mehran AhmadlouJanou H. W. HoubaJacqueline F. M. van VierbergenMaria GiannouliGeoffrey-Alexander,
GimenezChristiaan van WeeghelMaryam DarbanfouladiMaryam Yasamin ShiraziJulia DziubekMejdy KacemFred
de WinterJ. Alexander Heimel. Science, 372 (6543), eabe9681.

Systems neuroscience of curiosity.

Roberto Lopez Cervera, Maya Zhe Wang, Benjamin Y Hayden. Current Opinion in Behavioral Sciences 2020,
35:48–55

Daniel Berlyne (1924-1976) was the pioneer of the studies on curiosity. He believed that curiosity – the intrinsic
desire to acquire new knowledge and new sensory experience – is a key factor for learning and memory in
everyday life. Based on the attached review and article, you will propose a thesis project that would explore further
the function of a brain circuit of your choice in novelty seeking and curiosity. Using classical or more atypical
animal models, you will elaborate a 3 years thesis project, helping to better understand the circuits responsible
for curiosity and how curiosity may influence learning, enhances memory and/or confer neuropsychiatric disease
vulnerability.

D. Topic 4: Neuropatholgy, human research

Impact of circadian and diurnalrhythms on cellular metabolicfunction and neurodegenerativediseases

International Review of Neurobiology, Volume 154#2020 Elsevier Inc.ISSN 0074-7742All rights reserved.
https://doi.org/10.1016/bs.irn.2020.02.005

Based on the review of Smith and Musieck (2020) and using an experimental model and a methodology of your
choice, you will present a three-year Ph.D. project allowing a better understanding of the interaction
between biological rhythms and cellular metabolism in the onset and progression of neurodegenerative diseases.

8. Oenology

Effect of Agronomic Techniques on Aroma Composition of White Grapevines: A Review

Eleonora Cataldo*, Linda Salvi, Francesca Paoli, Maddalena Fucile and Giovan Battista MattiiAgronomy 2021,
11, 2027.
https://doi.org/10.3390/agronomy11102027

In the context of climate change, the aromatic quality of wines is increasingly affected by more and more extreme
abiotic factors. This quality is dependent on the quality of the berries and also on the fermentations.

Based on this research topic regarding the influence of viticultural practices on the aroma quality of grape berry
and wine, you will proposea PhD project to improve the knowledge on the impact of viticultural practices on
molecules of oenological interest which are responsible of the wine organoleptic quality(aromas, organic acids,
phenolic compounds, ...). These wine metabolites with organoleptic properties or hygienic properties can be
present in grape berries or produce during the pre-fermentation, fermentation or aging of the wine. You will
develop the mechanistic aspects from a biochemical, microbiologicalor wine making processes point of view.

9. Physiology

A. Physiologie générale

Mechanisms and physiological implications of cooperative gating of clustered ion channels

Dixon et al., 2022, Physiol Rev 102:1159-1210
https://doi.org/10.1152/physrev.00022.2021

Ion channels play a central role in the regulation of nearly every cellular process. A growing body of evidence
suggests that many ion channels do not gated independently, as originally assumed. Rather, cooperative gating
seems to be a general phenomenon that modulates multiple physiological processes in excitable and non-
excitable cells. Thus, alteration of this cooperative gating may be a key underlying factor modulating many cell
and organ functions in health and disease, which remain to be completely elucidated.

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 Inspired by the proposed review, you will develop a PhD project on the implication of cooperative gating of ion
channels in the pathology of your choice. This virtual thesis will involve various experimental strategies, both in
vitro and in vivo, and will have to be realized in 3 years.

B. Physiologie (cardiologie et maladies respiratoires)

Mohan A, Agarwal S, Clauss M, Britt NS, Dhillon NK. Extracellular vesicles: novel communicators in lung
diseases. Respir Res 2020; 21: 175.
Berezin AE, Berezin AA. Extracellular Endothelial Cell-Derived Vesicles: Emerging Role in Cardiac and Vascular
Remodeling in Heart Failure. Front Cardiovasc Med 2020; 7: 47.
Konkoth A, Saraswat R, Dubrou C, Sabatier F, Leroyer AS, Lacroix R, Duchez AC, Dignat-George F. Multifaceted
role of extracellular vesicles in atherosclerosis. Atherosclerosis 2021; 319: 121-131.

Extracellular vesicles (EVs) are small vesicles released by the majority of cells in response to cell activation. EVs
carry a diversity of bioactive molecules (proteins, mitochondria, lipids and genetic material). They are released
into the extracellular space and are therefore involved in pathophysiological pathways of cell-cell communication.

Inspired by the proposed reviews (1-3), you will develop a PhD project on the implication of extracellular vesicles
in a specific aspect of a cardio or respiratory pathology of your choice.

This virtual thesis will involve various experimental strategies, both in vitro and in vivo, and will have to be realized
in 3 years. For this virtual thesis project, we will consider that human samples from patients with and without the
chosen disease are available and could be part of the experimental strategies.

10. Plant biology

Plant responses to multifactorial stress combination

Sara I. Zandalinas and Ron Mittler
Department of Agricultural and Environmental Sciences, University Jaume I, Av. de Vicent Sos Baynat, s/n,
Castell_o de la Plana 12071, Spain; Division of Plant Sciences and Interdisciplinary Plant Group, College of
Agriculture, Food and Natural Resources, Christopher S. Bond Life Sciences Center, University of Missouri, 1201
Rollins Street, Columbia, MO 65201, USA New Phytologist (2022) 234: 1161–1167 doi: 10.1111/nph.18087

Summary
Human activity is causing a global change in plant environment that includes a significant increase in the number
and intensity of different stress factors. These include combinations of multiple abiotic and biotic stressors that
simultaneously or sequentially impact plants and microbiomes, causing a significant decrease in plant growth,
yield and overall health. It was recently found that with the increasing number and complexity of stressors
simultaneously impacting a plant, plant growth and survival decline dramatically, even if the level of each individual
stress, involved in such ‘multifactorial stress combination’, is low enough not to have a significant effect. Here we
highlight this new concept of multifactorial stress combination and discuss its importance for our efforts to develop
climate change-resilient crops.

In the context of developing new stress-tolerant varieties, you are invited to propose a PhD project (3 years)
addressing in a plant of your choice, a particular response (developmental, metabolic, or affecting other
phenotypic traits) to the combined effect of two relevant stresses of your choice (biotic and/or abiotic). Beside the
descriptive approach, you will aim at understanding the underlying mechanisms or genes by using the strategies
of your choice (cell biology, biotechnology, omics techniques, genetics, imaging techniques etc.). The scientific
approach(es) should be original and should provide new knowledge, material or tools that could be used in
agriculture.

11. Nutrition

Nutrigenomics: Epigenetics and cancer prevention: A comprehensive review

Ayesha Nasir, Mir. M. Hassan Bullo, Zaheer Ahmed, Aysha Imtiaz, Eesha
Yaqoob, Mahpara Jadoon, Hajra Ahmed, Asma Afreen & Sanabil Yaqoob (2019): Nutrigenomics:
Epigenetics and cancer prevention: A comprehensive review, Critical Reviews in Food Science and
Nutrition, DOI: 10.1080/10408398.2019.1571480
https://doi.org/10.1080/10408398.2019.1571480

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 Some bioactive food compounds, such as dietary polyphenols, have proven their efficacy in cancer prevention
through nutrigenomics mechanisms. The proposed review summarizes data regarding the role of nutrigenomics
in the prevention of diet- and lifestyle-related diseases, including cancer.

From this review, you will formulate a 3-year PhD research project that investigate the efficacy of a particular
nutritional strategy for the prevention of cancer through a nutrigenomics action

12. Bioinformatique

Design and synthesis of a minimal bacterial genome.

Ref. Hutchison CA 3rd, Chuang RY, Noskov VN, Assad-Garcia N, Deerinck TJ, Ellisman MH, Gill J, Kannan K,
Karas BJ, Ma L, Pelletier JF, Qi ZQ, Richter RA, Strychalski EA, Sun L, Suzuki Y, Tsvetanova B, Wise KS, Smith
HO, Glass JI, Merryman C, Gibson DG, Venter JC. Science. 2016 Mar 25;351(6280):aad6253. doi:
10.1126/science.aad6253. PMID: 27013737

Impact of large-scale engineering of genomes on their spatial structure, replication and expression of
genes

Construction of bacteria and other organisms with a completely or partially synthetic genome raises up the
question of the impact of large genome re-organizations on the spatial structure of chromosome(s), their
replication and the expression of the genes. This question is particularly important for building “chassis” organisms
which genomes have been reduced or widely shuffled for biotechnological applications.

You will propose a 3-year PhD project to better understand the impact of large-scale engineering of genomes on
their spatial structure, replication and expression of genes. For this, you will use a model organism which genome
can be easily engineered at a large scale. Your approaches will mainly rely on high throughput sequencing
technology-based methods.