Delphine Joseph: The alchemy of teamwork
Delphine Joseph is a researcher in pharmaco-chemistry at the Université Paris-Saclay Faculty of Pharmacy and director of the University's Graduate School of Health & Drug Sciences. In the Biomolecules: conception, isolation, synthesis laboratory (BioCIS - Université Paris-Saclay, CNRS, Univ. Cergy-Pontoise), of which she is the deputy director, Delphine Joseph co-directs the Chemistry of Natural Substances team. Between her research activities related to tobacco addiction or drug allergies, her involvement in the Université Paris-Saclay bodies and her institutional investment, we have an image of a researcher committed to serving the community.
Passionate about science from an early age, Delphine Joseph embarked on a course of study at the University of Metz at the interface between chemistry and biology, then specialised with a master's degree in molecular physical chemistry. During her thesis on anti-cancer drugs, the researcher spent two long periods abroad in an industrial environment, the first with the Italian pharmaceutical group Menarini in Barcelona, on the creation of beta-2 adrenergic receptors’ agonists with bronchodilator properties used in the treatment of asthma; the second in Basel, with the Swiss group Novartis, on the synthesis of herbicides of natural origin. Delphine Joseph obtained her PhD in 1995 and then went on to do a post-doc at the Université catholique de Louvain (Catholic University of Leuven) in Belgium with Professor Léon Ghosez who became her research mentor. “He immediately trusted me and taught me a lot about people management,” the researcher recalls. She then worked for two years on the development of a new method of synthesising antihistamines in collaboration with UCB Pharma.
Delphine Joseph has excellent memories of this period and “solid research friendships”, which she has made at Université Paris-Saclay. “Throughout my studies and my career, I have met some very nice people who have given me wonderful opportunities,” she says. In September 1998, she obtained a position as a lecturer in organic chemistry at the Faculty of Pharmacy of Université Paris-Saclay in Châtenay-Malabry.
Nicotine addiction
Delphine Joseph's research in BioCIS lab is at the interface of chemistry and biology. For the past ten years, she has been studying nicotinic receptors in collaboration with the Institut Pasteur as part of two projects funded by the French National Research Agency (ANR). The stakes are high: the aim is to treat tobacco addiction, the number one avoidable risk factor for cancer. “We are studying the functioning of a family of receptors involved in tobacco addiction in order ultimately to design molecules for therapeutic purposes. The aim is to understand at the molecular level the factors that govern the global movements of these receptors, in order to develop molecules capable of controlling them and inducing targeted pharmacological effects.” After studying a bacterial receptor, the second phase of the project directly targets a particular interface of a human receptor. “We are trying to design ligands for this orphan interface using a medicinal chemistry approach called 'de novo',” the researcher explains. Her team is now obtaining very encouraging results with the first active molecules.
The genius of many expertises
“It is thanks to the combination of skills in biology, bioinformatics and chemistry that the story was possible,” Delphine Joseph explains. “All our initial hypotheses finally converged thanks to everyone's expertise. Using natural substances from a blind screening and a series of molecules with proven nicotine activity, the chemists developed a library of fragments by cutting them into small compounds ready to be reconnected to each other. This bank was then screened in silico on molecular models of the receptor developed by bioinformaticians, and in vitro by various complementary biophysical methods using a model protein developed by neuropharmacologists,” the researcher explains. From the fragments that bind most effectively to the protein, chemists were able to design the first ‘hit’ molecules, or active molecules.” Next steps: their co-crystallisation before a potential valorisation, “within a year”, Delphine Joseph hopes.
Drug allergy
The other aspect of Delphine Joseph's research concerns the allergy to the muscle relaxants used in many surgical operations, including Covid-19 therapy. With her multidisciplinary team, the researcher is trying to understand the molecular mechanisms of this allergy as part of a project financed by the French National Agency for Food, Environmental and Occupational Health Safety (ANSES). This study is being carried out in connection with cohorts of professionals who are regularly confronted with quaternary ammoniums in the course of their work (hairdressers, disinfectants or cleaners), and who are therefore more likely to develop allergic reactions. “We have several hypotheses with very interesting results,” the researcher says. “In particular, we have shown that a drug and some cosmetic components were able to activate lymphocytes. We use biomimetic conditions to understand their metabolism and protein binding in vivo.” Delphine Joseph is pleased with the promising results. Ultimately, the aim is to develop a diagnostic strategy to prevent anaphylactic shock or to guide the choice of curarising agent.
Working for future generations
As soon as she arrived at the Faculty of Pharmacy, Delphine Joseph became involved in the reform of organic chemistry courses and joined the CNRS national committee. This investment in the University's community has continued ever since, until her arrival in July 2020 as head of the Graduate School of Health & Drug Sciences. This Graduate School brings together teaching and research teams from university departments (Faculties of Medicine and Pharmacy of Université Paris-Saclay), associate member universities (UVSQ and Université d'Évry) and partner research organisations (CNRS, Inserm, CEA and INRAE), around themes centred on drugs, health products and therapeutic innovation. “Our objective is to offer cutting-edge training through excellent research to meet societal challenges and the needs of industry.” There is no shortage of projects: a back-to-school event mixing incoming and outgoing classes, research days to combine expertise and give rise to interdisciplinary projects, etc.
Delphine Joseph fully supports the Université Paris-Saclay project. “Basic, translational and clinical research, and companies: all the ingredients are there to promote innovation,” she says. “It is true that this project requires a huge investment, but I do not forget that it is for the benefit of future generations. We have a huge responsibility to train critical, open and constructive minds through research.” It is no coincidence that Delphine Joseph takes great pride in the PEPS (Passion for Teaching and Pedagogy in Higher Education) award from her teaching team. Inspired by her own family, her unconditional support, the researcher believes that it is essential to adapt to new generations.
