Master 2 IBIS Therapeutic Engineering and Bioproduction in Biotechnology-Health

Teaching module focused on the professional world, with general introductions to predefined topics targeting the biotechnological exploitation of microorganisms (antimicrobials, microbiota, probiotics, applied virology, etc.), followed by presentations by industry professionals who come to talk about their career paths, their companies, and/or the development of a project. This teaching unit covers red biotechnologies (health applications) as well as other colors of biotechnology (green/agronomy, blue/marine, white/industrial, yellow/environmental).

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Within biotechnology, the production of recombinant proteins in various prokaryotic and eukaryotic expression systems represents a mature and attractive technological field with high employability. It is also a very important area of research in which many challenges remain to be addressed. The bioproduction of biomedicines (recombinant proteins as well as monoclonal antibodies) represents a major challenge in human therapeutics, but also in many areas of biotechnology (environmental, industrial, agronomic, marine, etc.). Before designing any biological drug involving a bioproduction stage, it is essential to understand the different eukaryotic and prokaryotic expression systems used in biotechnology and to have a comprehensive overview of the landscape and challenges of bioproduction in France, Europe, and around the world.

This course unit includes interactive lectures. It is taught by various academic and industry experts involved in the field.

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This EU presents the specific features of healthcare applications in the field of bioprocesses. Case studies on the production of biopharmaceuticals and innovative therapeutic drugs are provided (e.g., clinical-grade production of cell therapy products). The entire production chain is covered, with a particular focus on downstream processes (or DownStream Processing, DSP), which are particularly important for healthcare products (separation, extraction, purification, and even formulation operations). DSP represents a significant portion of production costs, and there are many expectations and challenges associated with these technologies, particularly with the development of single-use technologies. Upstream processing (USP) is covered in depth in the complementary teaching units of the Bioproduction specialization (HAV930V and HAV911V).

This course unit includes lectures and conferences with numerous presentations by industry professionals who will share their expertise and vision of the field with students. Beyond the technological aspects, these presentations will also provide an opportunity to discuss Good Manufacturing Practices (GMP), quality control, and the management of economic and environmental constraints.

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The commercialization of research into industrial applications will require strategies and stakeholders at the interface between the scientific and socio-economic worlds. Identifying and protecting the innovative nature of a discovery will be followed by the search for funding and partners to transform this idea into economic reality.

This course unit will focus on providing students with all the tools they need to promote their work with a view to discovering new therapeutic tools. This course unit includes lectures given by legal academics and professionals in the field, as well as a supervised project that runs throughout the course unit. Work will also be carried out in the Learning Lab: identifying innovative research, drafting a patent, developing a commercialization plan, creating a business, and developing a business plan.

This EU will involve university professors, industrialists, and professionals in the fields of patents and commercialization.

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Within biotechnology, bioprocesses involve the industrial application of living organisms (whether enzymes, microorganisms, or eukaryotic cells) for the synthesis of products of interest. This course will focus on the central stage of the bioprocess: biological reactions in reactors. More specifically, it will focus on the use of microbial and cellular catalysts. Products of interest may include fermented foods (wine, beer, etc.), energy molecules (bioethanol, methane, etc.), chemical intermediates, and biomedicines (vaccines, monoclonal antibodies, growth factors, etc.). The knowledge and skills acquired during this course unit will be transferable to any sector of activity. Examples will be given in the fields corresponding to the main career opportunities for the two programs concerned (Agrosciences and Health). This course is a direct continuation of the M1 HAV811V course "Bioprocess Engineering - Batch." It focuses on the UpStream Processing (USP) aspects of bioprocesses.

The first classes will provide an overview of bioprocesses and the approach applied in bioprocess engineering, as well as a brief review of batch mode (prerequisite for M1). The bulk of the course will then be devoted to the application of bioprocess engineering to reactors operated in continuous and Fed-Batch mode (or semi-(dis)continuous culture).

Cross-disciplinary modules will also be offered:

-Transfer management (management of mixing, heat transfer, gas transfer) with a strong focus on gas transfer and how to ensure the oxygen requirements of a culture (kLa, OUR, OTR).-Culture medium design

-Basic assessments (carbon footprint and redox balance)

-Development of an indicator for monitoring biological response: the Respiratory Quotient (RQ)

This course includes interactive lectures and tutorials.

An intensive practical application (1 month) in the form of a project is planned for students in the M2 Biology-Health/IBIS/specialization in bioproduction as part of the "Multidisciplinary lab project: from gene to protein" course units. For these students, a strong link is also planned with the specialization course units (HAV910V, HAV911V, and HAA910V). Please refer to the descriptions of these course units for more information.

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The multidisciplinary lab project, also called “Gene to Protein project”, will be a "learning by doing" project. The students will be in charge of the bioproduction of a protein using E. coli as a host. If they follow both parts of the project (1 & 2, like students from the Biohealth master's program), they will start with strain construction and continue with pilot-scale production and purification of the protein. Bioprocess engineering is a highly interdisciplinary field of study. The students (and future workers in the field) will benefit from project-based learning with an important practical component, where they can actively experience the interconnection between biology, engineering, and physical sciences.

Part 2 of the project will be dedicated to the "production process design and pilot scale production" of the recombinant protein using a high-cell density fed-batch culture. It will be a multidisciplinary, hands-on training course in Bioprocess Engineering and will be organized over three different periods:

-Week 1: In the Learning Lab, students will participate in workshops to design and plan a production process in accordance with available equipment and data (scientific papers, reports, websites, previous results from UE "Multidisciplinary Lab Project 1"). Based on the bottlenecks identified for the production of recombinant proteins in E. coli, students will choose the culture process to be used, define the production objectives, simulate the culture (planning objective), design a sampling plan, design the culture medium, etc.

-Week 2: In practical training rooms on pilot-scale equipment (20L working volume bioreactor), students will prepare the bioreactor and everything they need to perform the pilot-scale culture. They will be responsible for monitoring the culture and processing real-time data in order to detect and correct any deviations from the anticipated progress of the culture.

-Week 3: In learning labs, students will process and analyze the data. They will be responsible for interpreting and discussing the results and writing a professional report.

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