Periodic Reporting for period 1 - CryoEMatNOVA (CryoEM@NOVA: a cryo electron microscopy hub enabling drug discovery)
Période du rapport: 2023-01-01 au 2024-03-31
Structural biology is essential for atomic-level understanding of structure-function relationships in living systems and increasingly key to providing knowledge structure-based drug discovery. While traditionally the method of choice has been X-ray crystallography, in the past years, dramatic improvements of resolution using cryo electron microscopy (cryo-EM) have resulted in cryo-EM named 2015 Nature Method of the Year and the 2017 Nobel Prize in Chemistry. This in turn has had a major impact on the number of cryo-EM installations in Europe, publicly deposited structures, publications and related knowledge, teaching and dissemination.
Portugal was one of the few European countries without this technology. That is now changing with the inclusion of cryo-EM in the Portuguese Roadmap of Research Infrastructures 2020, resulting in major funding (€2.5M) for the first autoloader cryo electron microscope installed in Portugal in 2023, coordinated by the CryoEM-PT consortium in which UCIBIO-NOVA-FCT is a node. This presents an excellent opportunity for establishing cryo-EM research and training in Portugal, and specifically at NOVA-FCT, which has expertise using X-ray crystallography and NMR, while expertise in cryo-EM was lacking, resulting in unmet needs.
The overall objective of CryoEM@NOVA is to establish a sustainable cryo-EM hub for research and training at NOVA-FCT. Under the direction of the ERA Chair holder this objective is clearly achievable as Prof. Luecke has experience in setting up cryo-EM infrastructures leading to high-resolution structures of proteins with medically-relevant bound inhibitors, generating high-impact publications and attracting funding and collaborations.
The operation of advanced electron microscopes and associated vitrification robots coupled with storage- & compute-intensive data analysis requires scientists with in-depth knowledge & training. Such talent will have acquired this expertise elsewhere and is being recruited to Portugal.
Portugal was one of the few European countries without this technology. That is now changing with the inclusion of cryo-EM in the Portuguese Roadmap of Research Infrastructures 2020, resulting in major funding (€2.5M) for the first autoloader cryo electron microscope installed in Portugal in 2023, coordinated by the CryoEM-PT consortium in which UCIBIO-NOVA-FCT is a node. This presents an excellent opportunity for establishing cryo-EM research and training in Portugal, and specifically at NOVA-FCT, which has expertise using X-ray crystallography and NMR, while expertise in cryo-EM was lacking, resulting in unmet needs.
The overall objective of CryoEM@NOVA is to establish a sustainable cryo-EM hub for research and training at NOVA-FCT. Under the direction of the ERA Chair holder this objective is clearly achievable as Prof. Luecke has experience in setting up cryo-EM infrastructures leading to high-resolution structures of proteins with medically-relevant bound inhibitors, generating high-impact publications and attracting funding and collaborations.
The operation of advanced electron microscopes and associated vitrification robots coupled with storage- & compute-intensive data analysis requires scientists with in-depth knowledge & training. Such talent will have acquired this expertise elsewhere and is being recruited to Portugal.
As the establishment of a cryo-EM hub for research and training is the central objective of the project, emphasis was given to the preparation of an infrastructure ready for protein purification and Cryo-EM sample preparation & data processing:
i) a space at NOVA-FCT campus was totally adapted allowing the setup of a functional laboratory where equipment dedicated to protein isolation and purification is being installed (a microplate reader with absorbance and fluorescence detection, a laminar air flow cabinet and other small equipment as micropipettes, desiccator, freezers, etc).
ii) for cryo-EM sample preparation, an isolated room was prepared to work under controlled temperature and humidity already equipped with:
- a hood for producing liquid ethane;
- a glow-discharger to turn the carbon-coated grids surface hydrophilic;
- a semi-automated vitrification robot to perform the cryo-fixation process;
- a cryo-shipper and shipping case for grids transport.
At the moment our researcher’s team is receiving training for the equipment’s handling and maintenance.
iii) the data process infrastructure is currently under planning; we are consulting experts in Cryo- EM software able to provide validated and certified GPU systems.
i) a space at NOVA-FCT campus was totally adapted allowing the setup of a functional laboratory where equipment dedicated to protein isolation and purification is being installed (a microplate reader with absorbance and fluorescence detection, a laminar air flow cabinet and other small equipment as micropipettes, desiccator, freezers, etc).
ii) for cryo-EM sample preparation, an isolated room was prepared to work under controlled temperature and humidity already equipped with:
- a hood for producing liquid ethane;
- a glow-discharger to turn the carbon-coated grids surface hydrophilic;
- a semi-automated vitrification robot to perform the cryo-fixation process;
- a cryo-shipper and shipping case for grids transport.
At the moment our researcher’s team is receiving training for the equipment’s handling and maintenance.
iii) the data process infrastructure is currently under planning; we are consulting experts in Cryo- EM software able to provide validated and certified GPU systems.
Our CryoEM@NOVA project will bring to Portugal a new hub of advanced cryo electron microscope technology providing access to world-wide researchers and students. This will fill a gap in Portugal's scientific capabilities and allow the study of atomic-level structure-function relationships in living systems.
By enabling researchers to better understand the structure of biological molecules at an atomic level, CryoEM@NOVA can lead to the design of new compounds with potential for drug development. This innovation can attract industry partnerships and collaborations, leading to the creation of new drugs and therapies that could greatly benefit patients. Additionally, the project's success in attracting funding and collaborations demonstrates its potential to make significant advancements in the field of medicine and pharmaceuticals.
We are establishing a research line at NOVA, focused on Prof. Luecke's project for Helicobacter pylori eradication based on structure-based drug development strategies. H. pylori infection is affecting approximately half of the global population and is a leading cause of peptic ulcer disease and gastric cancer. The development of lead compounds through this research has the potential to significantly impact both the economy and human health by providing therapeutics for bacterium eradication and reduction of associated diseases, including stomach cancer.
By enabling researchers to better understand the structure of biological molecules at an atomic level, CryoEM@NOVA can lead to the design of new compounds with potential for drug development. This innovation can attract industry partnerships and collaborations, leading to the creation of new drugs and therapies that could greatly benefit patients. Additionally, the project's success in attracting funding and collaborations demonstrates its potential to make significant advancements in the field of medicine and pharmaceuticals.
We are establishing a research line at NOVA, focused on Prof. Luecke's project for Helicobacter pylori eradication based on structure-based drug development strategies. H. pylori infection is affecting approximately half of the global population and is a leading cause of peptic ulcer disease and gastric cancer. The development of lead compounds through this research has the potential to significantly impact both the economy and human health by providing therapeutics for bacterium eradication and reduction of associated diseases, including stomach cancer.