PRR Project

Summary

Precision Medicine is a therapeutic strategy which, unlike the traditional " one-size-fits-all " approach, proposes a therapy tailored to the patient, taking into account genetic, phenotypic or psychosocial factors. The main goal is to improve the therapeutic effect, maximizing efficacy while minimizing adverse effects and toxicity. This methodology strongly depends on the existence of biomarkers as well as on target specific drugs and/or imaging agents, including patient´s particular disease-related mechanisms, with high selectivity and affinity. In this context, the Molecular Imaging/Systemic Radionuclide Therapy (Molecular Radiotherapy) combination is of unquestionable importance. Imaging techniques enable early diagnosis and the identification and stratification of patients based on the characteristics of the disease that share the same prognosis and similar response to treatment. Molecular imaging and radiotherapy allow for the visualisation, characterisation and assessment of biological processes at a molecular level and targeted, localized, treatment with radionuclides. Research activities in these scientific areas are characterised by their strong inter- and multidisciplinary nature, at the interfaces of chemistry, radiochemistry, (bio)physics, biology, (radio)pharmacy and medicine. The major challenges in these areas and their decisive contribution to Precision Medicine are related to the identification/characterisation of disease biomarkers and their validation as molecular targets for imaging and/or therapy, particularly with regard to their location and density of expression. In addition, the ability to design innovative agents with greater specificity and more appropriate pharmacokinetics, including molecular or "nano" platforms for imaging and therapy, generically known as theranostic agents , is key. The answer to the challenges mentioned above definitely involves the use of the new "state of the art" computational tools, which could play a decisive role both in the validation of new molecular targets/biomarkers and in the design of new radioactive agents with innovative properties for diagnostic imaging, targeted systemic radiotherapy and theranostics . It is in the context described herein that the proposal to open a strategic position in the area of Chemical and Radiopharmaceutical Sciences, more specifically in the sub-area of " Structural Biology and Computational Biophysics applied to Radiopharmaceutical Chemistry", is framed.The doctoral researcher to be hired should have solid postgraduate training in the use of ionising radiation in the context of life and health sciences and, preferably, recognised experience in the use of computational methods. The latter should be applied to the study of relevant targets (e.g. cell membrane receptors of the GPCR family or tyrosine kinases) and to the design of new molecular (e.g. small molecules or metal complexes) or “nano” (e.g. nanoparticles of various types) agents for applications in imaging, molecular radiotherapy or cancer theranostics. Computational methods have made a significant contribution to drug design, in particular due to easy access to experimental data. The importance of revealing the interaction network of human proteins is undeniable, particularly with regard to identifying new molecular targets. The compatibility of the target site of the active protein with the small molecule or/ligand or/ nanoparticle is assessed, so that more effective agents can be designed. Molecular docking and molecular dynamics simulations of biostructures can be used to guide the research. Computational models expose the dynamics involved in the interaction of compounds with the molecular target. Therefore, having the knowledge of how proteins interact with each other will provide a great opportunity to understanding pathogenic mechanisms, and subsequently support the development of radiopharmaceuticals targeted to specific disease pathways. As mentioned above, the Auxiliary Researcher to be hired should be able to demonstrate their scientific autonomy in recent years, have a high level of internationalization and a relevant number of books/book chapters and publications in peer-reviewed international journals of the specialty. He/she is expected to develop science of excellence, foster advanced education activities and leverage funding opportunities from national and European agencies and industry.Contrary to other schools at the University of Lisbon, the number of researchers at IST who use computational chemistry tools to meet the specific challenges in drug development is scarce. Therefore, hiring a PhD researcher to develop scientific projects that combine an experimental strategy on application of ionising radiation to life and health sciences with computational chemistry tools would definitely be an asset for DECN and C2TN for the development of new skills in emerging areas at IST.