Topics

The goal of LERMIT is thus to foster interdisciplinary research at the interface between chemistry, physico-chemistry and biology. Organizing the research around this main objective was not an easy task and required heavy brainstorming and stimulating discussions. As a result, we decided to organise the research within LERMIT around three main topics.

The first topic – TARGETS - aims at identifying and validating new therapeutic targets in the three classes of diseases listed above. This includes discovery of molecular mechanisms, proof of concept in cellular and animal models, screening of chemical libraries, validation and chemical optimization of the hits, preliminary ADMET and drugability tests, molecular modelling, evaluation of the lead molecules in animal models, etc. Three specific projects are proposed below to find new drugs to fight against 1) cardiovascular diseases (T1), 2) inflammation and immune deficiency (T2) and 3) cancer (T3).

The second topic – RESISTANCE - aims at identifying new strategies to get around the reduction in effectiveness of a drug in curing a disease. This concerns obviously the resistance to antimicrobial and anti-cancer drugs, but also more recently the resistance to immunotherapies. Resistance involves molecular mechanisms, such as mutation of the target enzyme or its relocation. Identifying these mechanisms allows a predictive structural pharmacological approach and the design of new and more efficient drugs. Two specific projects are proposed, one is to fight the antibiotic-resistant Gram-negative bacteria (R1), and the other to overcome biotherapy treatment failure in patients with rheumatoid arthritis (R2).

The third topic – DELIVERY – aims at designing new delivery systems, mainly nano and microtechnologies, to improve i) drug delivery to the right target and avoiding broad distribution that induce toxicity, ii) protection against degradation, and iii) drug transport across biological barriers. Because of a strong expertise within LERMIT in the field of cardiovascular diseases, we propose an innovative and ambitious interdisciplinary project to target the cardiovascular sphere and the pulmonary vasculature (D1).