Prof. Helena Danielson (UU), Dr. Wolfgang Jahnke (NOVA)
Using binding kinetics for drug discovery
About the project:
American and African Trypanosomiasis are neglected and infectious diseases that affect millions of people each year in the southern hemisphere. Uppsala University’s role in AEGIS project is the study of farnesyl pyrophosphate synthase (FPPS). FPPS is an enzyme involved in the mevalonate pathway that synthesizes essential components for reproductive cell cycle and grows in Trypanosoma Cruzi (American T.) and Brucei (African T.), as well for Leishmania. This enzyme represents therefore a validated target for the mentioned parasites.
The aim is to optimize lead compounds by in-depth characterization of molecular interactions using SPR biosensor technology and orthogonal methods. The project will focus on inhibitors of FPPS from three different species (T. Brucei, T. Cruzi and human). It will involve the development of several biochemical and biophysical assays and using them for screening of fragments and characterizing hits and leads.
Born in Magenta (Milano), I approached the scientific world with a MSc in Pharmaceutical Chemistry and Technology (2014) at Piemonte Orientale University (UPO) in Novara, Italy. I carried through my experimental thesis project in the Structural Biochemistry lab of Prof Menico Rizzi. I then joined Dr Alberto Massarotti’s group for a fellowship in Computational Biochemistry (UPO). I finally joined the AEGIS project, inspired by the challenges and opportunities that it represents.
PUM 3 months
List of publications:
Establishing Trypanosoma cruzi farnesyl pyrophosphate synthase as a viable target for biosensor driven fragment based lead discovery. Opassi G, Nordström H, Lundin A, Napolitano V, Magari F, Dzus T, Klebe G, Danielson UH; Protein Science 2019, accepted. DOI: 10.1002/pro.3834
The hitchhiker’s guide to the chemical-biological galaxy. Opassi G, Gesù A and Massarotti A; Drug Discov. today, 2018, Vol. 23, Issue 3, 565-574. DOI:10.1016/j.drudis.2018.01.007
List of posters:
Casting light on fragment hits identified by SPR analysis: a luminescent assay for validation of Farnesyl Pyrophosphate Synthase inhibitors, NovAliX Conference – Biophysics in Drug Discovery, June 8th 2017, Strasbourg, France
List of presentations:
Targeting Chagas disease using fragment-based lead discovery: validation and screening of FPPS enzyme.
XXVI National Meeting in Medicinal Chemistry, Jul 16-19, 2019, Milano, Italy
Faculty of Science and Technology
Dept. of Chemistry - BMC
SE-751 23 Uppsala