Multidisciplinary internship offer
Innovative eco-friendly biopesticides inspired by spider toxins: synthesis and 3D structure determination
Drs. Baptiste Legrand and Sebastien Dutertre, in collaboration with Drs. Pascal Verdié and Pierre Charnet, Institut des Biomolécules Max Mousseron (IBMM).
6 months internship (M2/Engineering School) Chemistry/Biophysics – starting january-march 2024.
Background:
The world population is projected to reach 9 billion by 2050, likely adding pressure on the agricultural community to increase crop production (Urritia et al. 2022). Increasing the productivity of existing farmlands can be achieved by reducing losses due to insect pest activity which destroys ~15% of the world’s annual production and damages an additional 20% of stored food grains (Windley et al, 2012). Consequently, the destruction of insects through the use of pesticides provides significant economic benefits (Goulson et al, 2015).
Project:
However, current pesticides have significant environmental impacts and together with the health-related concerns over their widespread use, many countries have now restricted their application. Therefore, there is an urgent need to develop alternative approaches to gradually replace the use of pyrethroids and neonicotinoids, the most widely used insecticides. The acute toxicity of these small molecules is due to the non-selective targeting of key ion channels. As alternatives to small molecule insecticides, cysteine-rich peptides found in venoms are stable and effective as insecticides in agricultural applications, as well as being health/environmentally benign (see company Vestaron, https://www.vestaron.com/). Interestingly, some spiders prey exclusively on pollinators, while others are exquisitely selective for insect pests. Thus, spider venoms are unique reservoirs of highly potent and selective toxins for channel subtypes, providing a strong basis for the development of innovative biopesticides. In this context, we propose to 1) study the structure-activity relationship of toxins targeting key ion channel subtypes of honeybee and insect pests, and 2) develop innovative bioinspired approaches to specifically target the insect pests.
Candidate:
Thus, the M2 student will have the opportunity to integrate a multidisciplinary project with all participants being localized at the IBMM (Montpellier). We have selected 2 peptide sequences from spiders which target the honeybee ions channels, and 3 others from spiders which hunt only insect pests. 1) First, (s)he will synthesize these 5 toxins using standard SPPS methods. Then, (s)he will fold, purify and characterize the peptide sequences by HPLC and by LC-MS. 2) Finally, (S)He will assign the chemical shifts of at least one toxin and determine its 3D structure by NMR. The candidate must have a solid foundation in peptide chemistry and structure determination as well as a strong interest in pharmacology as the bioassays on the activity of the peptides will be performed during the internship.
Please do not hesitate to contact us for further information.
*This project is funded by Pôle Chimie Balard “Bourses de stages Master 2 2024-2025”.
