Workshop: Spatial Multi-Omics for Mapping Human Tissue Function, Aging, and Diseases

On Monday, June 17, Restore lab receives Rong Fan, Ph.D. from Department of Biomedical Engineering, Yale University at 2pm for a talk about “Spatial Multi-Omics for Mapping Human Tissue Function, Aging, and Diseases“.

Despite latest breakthroughs in single cell sequencing that revealed cellular heterogeneity, differentiation, and interactions at an unprecedented level, the study of multicellular systems needs to be conducted in the native tissue context defined by spatially resolved molecular profiles to better understand the role of spatial heterogeneity in biological, physiological and pathological processes. In this talk, I will begin with discussing the emergence of a whole new field – “spatial omics”, and then focus mainly on a new technology platform called Deterministic Barcoding in Tissue (DBiT) for spatial omics sequencing developed in our laboratory over the past years. We conceived the concept of “spatial multi-omics” and demonstrated it for the first time by co-mapping whole transcriptome and proteome (~300 proteins) pixel-by-pixel directly on a fixed tissue slide in a way compatible with clinical tissue specimens including FFPE. It has been applied to the study of developing mouse brain, human brain, and human lymphoid tissues associated with normal physiology, disease, or aging. Recently, our research enabled another new field – “spatial epigenomics” – by developing multiple DBiT-based spatial sequencing technologies for mapping chromatin accessibility (spatial-ATAC-seq), histone modification (spatial-CUT&Tag), or further combined with transcriptome or proteins for spatial co-profiling. These new technologies allow us to visualize gene expression regulation mechanisms pixel by pixel directly in mammalian tissues with a near single cell resolution. The rise of NGS-based spatial omics is poised to fuel the next wave of biomedical research revolution. Emerging opportunities and future perspectives will be discussed with regard to human biology research, aging, disease, clinical biomarker discovery and therapeutic development

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Biosketch

Dr. Rong Fan is the Harold Hodgkinson Professor of Biomedical Engineering at Yale University and Professor of Pathology at Yale School of Medicine. He received a Ph.D. in Chemistry from the University of California at Berkeley and completed the postdoctoral training at California Institute of Technology before joining the faculty at Yale University in 2010. His current interest is focused on developing microtechnologies for single-cell and spatial omics profiling to interrogate functional cellular heterogeneity and inter-cellular signaling network in human health and disease (e.g., cancer and autoimmunity). He co-founded IsoPlexis, Singleron Biotechnologies, and AtlasXomics. He served on the Scientific Advisory Board of Bio-Techne. He is the recipient of a number of awards including the National Cancer Institute’s Howard Temin Career Transition Award, the NSF CAREER Award, and the Packard Fellowship for Science and Engineering. He has been elected to the American Institute for Medical and Biological Engineering (AIMBE), the Connecticut Academy of Science and Engineering (CASE), and the National Academy of Inventors (NAI).    

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Interview of the CARe Graduate School, Philippe Valet by SANAO (association representing healthcare companies in Occitania)

Translation of the video:

What is the goal of the CARe doctoral school ?

Nowadays, Biology or research in Biology or bio-medicine research can no longer be achieved by  biologists only. It’s over. That was the case when i first start to do research.

Now, we need informaticians obviously. We also need mathematicians, , physicians, chemists… At the University where I used to be Director of Masters or Director of the PhD School for a long time, tracks are quite fixed. That is to say : when you study immunology, you do immunology, when you study cancerology, you do cancerology, I used to study Pharmacology, I do pharmacology and nothing else.

I think this is over now, it cannot work that way anymore. Tracks must be mixed, merged and have to overlap. The idea of CARe is simple : gathering  everybody no matter if they are researchers, as we are here in the lab « the laboratory rats », or clinician, or engineers, -lots of engineers are applying to the Care program by the way- or private companies and make everybody work together.

The CARe PhD School is a graduate school, could you explain us what it is ?

The Graduate School starts from the Master to the PhD. It is a five-year educational program that includes first year of Master, second year and PhD program.

Is it possible to go abroad ?

So during the first semester of Master 1, students stay here (in Toulouse) but they are free to go abroad as soon as the second semester. One of the main principle of CARe is to spend some internship time abroad. For a minimum of 3month to a maximum of 6 months funded by CARe-GS. If they want to stay longer, their host laboratory have to take care of the extra-funding.

How are the lessons schedulded ?

During the second year of Master, teachings are planned on the afternoons, and in English obviously. They are done in visioconference. We have  a fully-connected room. A very interactive room, not just a visio link on a computer.

During the first year of Master, they have lessons on Monday, Tuesday until Wednesday noon –even if their schedule is not always full- but that is a maximum. The rest of the week they are in the labs, all year long. They are not disconnected from the labs and that is great.

What is the difference with a classic training program ?

The difference with a classic training program is that for example, Master 1 students are doing 2-months internships, Master 2 students are doing 4-monhs internships or something like that. At the CARE GS, students are doing their internship since day 1, all year long.

At the end of their training program, which diplomas do the PhD students get ?

They get a double-diploma : one from the University toulouse III- Paul Sabatier, one from the other university, from Gottingen etc. So they graduate with a PhD double diploma more a diploma supplement that is given by the CARe Graduate School, soi t is valuable on their resumes.

How many students do you have by classes ?

They are 15. Half of them are international students, CARe is funding their travel and accomodation.

Do you have any advices for high schools students ?

No matter what you are keen on, just do things you like. If it is biology, study biology, if it is mathematics, do mathematics, do something you love.

INTEGRATING MULTI-OMICS AND BIOLOGICAL KNOWLEDGE TO BRIDGE SIGNALLING AND METABOLISM

On Friday, March 22nd, Aurélien Dugourd from the Saez-Rogriguez lab, Heidelberg University will give a talk on how the integration of multi-omics and biological knowledge can bridge signalling and metabolism at 11am in Salle Cazaux, CRCT.

BIO: After he graduated from his Computational Biology master’s degree in 2015, Aurelien Dugourd joined Julio Saez-Rodriguez team as a PhD student. He worked on the development of hybrid mechanistic models, integrating gene regulation, signaling pathways and metabolomics data to explain disease phenotypes, help find new therapeutic targets and predict their potential effect based on a specific patient profile. This led to the development of the tools COSMOS and oCEan. This project was part of the collaborative SyMBioSys ITN project, financed by the European Marie Skłodowska-Curie actions, as well as the SMART-CARE consortium to apply mass-spectrometry-based systems medicine to cancer.
Today, he leads the development and application of methods to extract interpretable mechanistic insights from multi-omic datasets. He especially focuses on leveraging prior knowledge, in the context of signaling and metabolism of complex diseases, such as cancer and development of treatment resistance. He works in collaboration with pharmaceutical partners, notably Pfizer, to support the development of novel cancer treatments and better understand the development of resistances by bringing those methods closer to relevant industrial applications.

Follow the event online here.

Our 2024 call for PhD proposals is open

2024 Call for PhD proposals

 

The CARe Graduate School’s PhD program is devoted to the training of students in multidisciplinary research topics, from basic science to clinical or pharmacological applications, with a focus on cancer, ageing and/or rejuvenation. PhD research projects are directed by CARe-associated research teams from academic laboratories or partner companies. The EUR CARe PhD program selection will have two phases:

Phase 1: PhD pre-proposals will be submitted to Claire Mendoza (claire.mendoza-berrio@univ-tlse3.fr) and Clemence Grosnit (clemence.grosnit@univ-tlse3.fr) using this template, before evaluation and selection by the CARe Scientific Committee. Deadline for application is March 1st, 2024.

The applications must fall in the field of cancer, aging and/or rejuvenation. In addition, multidisciplinary is highly recommended and proposals must be at the interface of biology and mathematics, computer science, chemistry or physics. Examples are: mathematicians addressing complex biological questions by developing new molecules, tools, technologies or models, possibly doing some bench work, or biologists trained in mathematics, physics, computer sciences, advanced bioinformatics to develop new strategies that would be later questioned/validated in experimental biological settings…

Partnerships between teams from different doctoral schools, and/or foreign universities or industry are strongly encouraged (see scoring below). A short internship abroad (3 to 6-month) is mandatory, the nature of which should be briefly mentioned at this step. The travel and accommodation will be funded by the CARe program.

The scoring system (out of 10) is the following: 

  • Scientific quality of the proposal (5 points)
  • Co-supervision & interdisciplinarity (options 1 to 3 are not cumulative)
    1. If the project involves co-supervision by two teams working on different themes, each affiliated to a distinct disciplinary doctoral school : 2 points (lowest score)
    2. Or if the project includes co-supervision with an industry partner or a foreign university : 3 points (middle score)
    3. Or if the project involves co-supervision with an industry partner or a foreign university, spanning two interdisciplinary fields : 5 points (highest score).

NB: the candidates should not be formally identified at this step.

Upon acceptance, the proposers will be informed on March 11th, 2024, and the proposals will be posted online on CARe’s website and social networks.

Phase 2: PhD candidates for the pre-selected projects will submit the full proposal to Claire Mendoza (claire.mendoza-berrio@univ-tlse3.fr) and Clemence Grosnit (clemence.grosnit@univ-tlse3.fr) using the template that will be made available on CARe’s website.

At this step, PhD candidate must be identified and are asked to send a complete CV. In addition, it is mandatory to provide a full description of the 3-6 months internship, including a signed attestation from the hosting foreign university or from industry.

The files must be submitted as a single PDF before May 10th, 2024. Applicants will defend their proposal in early June 2024, in front of a jury representative of the CARe Graduate School, with delegates from Toulouse partner doctoral schools.

The audition will consist of 12 minutes of presentation and 15 minutes of questions. The presentation and the answers to questions have to be done in English.

The presentation must include, in this order, 1 title slide, 1 slide presenting the candidate, one slide presenting a previous research experience. The rest of the slides are dedicated to the presentation of the project (scientific justification of the research project, strategy, methodology, feasibility and risk management), including a description of the internship abroad or in industry. The following criteria will be evaluated by the jury: discussion of a previous research experience, quality of the oral presentation and of the response to questions.

SYMPOSIUM: Computational approaches for predictive immunotherapy

On Thursday December 21st, Dr Elana Fertig and Dr. Federica Eduati are giving a keynote lecture on Computational Sciences at IUCT-Amphitheater from 2pm to 4pm.

Dr Elana Fertig advances a new predictive medicine paradigm for oncology by converging systems biology with translational technology development. Her computational cancer biology research is inspired by her background as a NASA fellow in weather prediction. She aims to invent computational techniques that use multi-platform high-throughput precancer and tumor datasets to forecast the cellular and molecular pathways of future cancer progression and therapeutic resistance. An authority in computational oncology, Dr. Fertig has been a leader in establishing spatial multi-omics technologies, matrix factorization, and transfer learning as current mainstays in bioinformatics. Her combined expertise in computational oncology, chaos theory, nonlinear dynamics, and tumor immunotherapy ensure translational relevance and mechanistic validation of computational findings. Beyond algorithm development, Dr. Fertig’s transdisciplinary expertise enables her to lead large-scale, team-science projects adapting cutting-edge molecular profiling technologies to human clinical trials to uncover new therapeutic interception pathways. Her transdisciplinary research has made her a sought after mentor and recognized leader of new training paradigms that converge oncologists, pathologists, basic biologists, computational investigators, and engineers to advance the next generation of computationally-driven oncology care.

Dr. Fertig is a Professor of Oncology and Division and Associate Cancer Center Director in Quantitative Sciences, Co-Director of the Convergence Institute, and Co-Director of the Single-Cell Training and Analysis Center at Johns Hopkins University. She has secondary appointments in Biomedical Engineering and Applied Mathematics and Statistics, affiliations in the AI-X Foundry, Institute of Computational Medicine, Center for Computational Genomics, Machine Learning, Mathematical Institute for Data Science, and the Center for Computational Biology and is a Daniel Nathans Scientific Innovator and MD Cancer Moonshot Senior Scholar. Prior to entering the field of computational cancer biology, Dr Fertig was a NASA research fellow in numerical weather prediction.

Dr. Fertig’s research is featured in over numerous peer-reviewed publications, R/Bioconductor packages, and competitive funding portfolio as PI and co-I. Notably, she led the team that won the HPN-DREAM8 algorithm to predict phospho-proteomic trajectories from therapeutic response in cancer cells and was elected to the College of Fellows American Institute for Medical and Biomedical Engineering (AIMBE) in 2022. She serves on the editorial boards of PLoS Computational Biology, Cell Systems, ImmunoInformatics, and Cancer Research Communications.

Dr. Federica Eduati earned her PhD in Biomedical Engineering in 2013 working on different computational modeling approaches to gain new insights into biological systems. She then became a postdoc (EMBL EIPOD, co-funded Marie Curie fellowship) at the European Molecular Biology Laboratory (EMBL), shared between the Systems Biomedicine group of Julio Saez-Rodriguez at EMBL-EBI (Cambridge, UK) and the microfluidics group of Christoph Merten at EMBL-HD (Heidelberg, Germany). During her postdoc she led pioneering work on developing predictive personalized models of intracellular signaling pathways of cancer patients, combining mathematical modeling and microfluidics technology development. Since 2018 she leads the Systems Biolgy for Oncology group at Eindhoven University of Technology (TU/e, The Netherlands) as tenured Assistant Professor. The work of her group is focused on understanding drug response in the tumor microenvironment using holistic approaches to improve precision (immuno)oncology.

Tumors are dynamic ecosystems shaped by a multitude of interacting molecules and cells. The heterogeneity observed in patients’ tumor development and treatment responses can be attributed to diversity in the underlying regulatory networks. In this presentation, I will illustrate how mathematical models can provide a nuanced description and understanding of the intricate relationship between a tumor’s composition and its behavior. Using mathematical models, we integrate general prior knowledge on possible interactions and patient-specific data to gain a mechanistic understanding of resistance/response to treatment in individual patients. This approach holds the potential to improve the way we personalize treatment based on patient’s molecular characteristic.

Title of the conference: “Computational modelling of the tumor and its microenvironment for precision oncology”

Abstract: Tumors are dynamic ecosystems shaped by a multitude of interacting molecules and cells. The heterogeneity observed in patients’ tumor development and treatment responses can be attributed to diversity in the underlying regulatory networks. In this presentation, I will illustrate how mathematical models can provide a nuanced description and understanding of the intricate relationship between a tumor’s composition and its behavior. Using mathematical models, we integrate general prior knowledge on possible interactions and patient-specific data to gain a mechanistic understanding of resistance/response to treatment in individual patients. This approach holds the potential to improve the way we personalize treatment based on patient’s molecular characteristic.

Please join online here.

Research and Technology National Agency (ANRT) “Pour un plan national en faveur du doctorat” with CARe’s Director, Philippe Valet

The conference “Pour un plan national en faveur du doctorat” (For a national plan to promote doctorates) was held on Friday 17 November at CampusCyber – La Défense, ¨Paris.
On this occasion, Sylvie Retailleau, Minister for Higher Education and Research, announced the launch of a mission on the doctorate, entrusted to Sylvie Pommier and Xavier Lazarus, which will be supported by the ANRT.
Philippe Valet, Director of the “Cancer, Ageing and Rejuvenation” Graduate School was invited to present the work and organisation of this new transdisciplinary international education program.
See Philippe Valet intervention here. (2:36:41 – 3:46:30)

Insights into the disruption of gene regulatory programs in cancers – Workshop by Anthony Mathelier

On October 20 from 11 to 12, Dr Anthony Mathelier from the Molecular Medecine Norway Center will give a workshop at the Toulouse Research Center in Cancerology

Abstract:

Most cancer somatic alterations occur in the noncoding portion of the human genome, which contains important cis-regulatory regions acting as genetic switches to ensure gene expression occurs at correct times and intensities in correct tissues. However, the identification of critical noncoding cancer driver events has been mostly limited to a few examples with high recurrence or high functional impact. Transcription factors (TFs) are key proteins binding to cis-regulatory regions at their TF binding sites to modulate the rate of gene transcription. As cancer is a disease of disrupted cellular regulation, it is critical to analyze these regions to highlight patient somatic mutations and epigenetic modifications altering the gene regulatory program of the cells. In this talk, I will present our recent works on the interplay between TF binding, somatic mutations, and DNA methylation alteration that shifts the gene regulatory program in patients cancer cells.

If you are willing to attend this event online, please join here.

HUMAN GENE THERAPY: FROM BASIC PRINCIPLES TO APPLICATIONS IN THE MUSCULOSKELETAL SYSTEM

On Thursday, October 12th, at 9AM, Magali Cucchiarini, Professor of Molecular Biology & Vice-Director, Center of Experimental Orthopaedics at the Saarland University Medical Center is giving a workshop at RESTORE lab on human gene therapy.

Magali Cucchiarini, PhD, is a Professor, Group Leader, and Vice-Director of the Center of Experimental Orthopaedics, Saarland University Medical Center, Homburg/Saar, Germany, involved in the teaching activities of the Medical Faculty of the Saarland University (Biochemistry and Molecular Biolo-gy). She graduated from the University of Nice-Sophia Antipo-lis, France (PhD, summa cum laude), worked at the University Hospital Inselsspital, Bern Switzerland, and was a senior scientist at Harvard Medical School. Her research interest is to generate innovative cell-, gene-, and tissue engineered-based systems to treat musculoskeletal diseases.

If you want to join online, click here

1st Young Scientist Cancer Congress (YS2C) -New Research for cancer therapy- from bench to bedside

October 5th, 2023

The CRCT postdocs association was created in 2022 by Benoît Aliaga, Chloé Bessière and Steffen Fuchs. It gathers the 31 postdocs who are currently present in the Cancer Research Center of Toulouse. They decided to organize the 1st Young Scientist Cancer Congress of the Cancéropôle Grand Sud Ouest (GSO) on the 5th October 2023 at the Oncopole, Toulouse.

Aim: The main goals of this day are to promote the work of the GSO postdocs and young clinician scientists, to network, and to optimize their career paths.
Public: To achieve our goals, we decided to open the conference to the whole scientific community of the GSO, which are researchers and clinicians of all career levels.
Organization: This day will alternate presentations by internationally renowned keynote speakers, presentations by postdocs from the GSO, an application-focused presentation by a leading single-cell sequencing company and a presentation from an editor of Nature Communications about scientific publishing and peer-reviewing.