Cancer is one of the most devastating diseases leading to millions of deaths per year, and cancer research is a major topic in many laboratories in academia and industry. The main goal in this proposal is to understand the biology of cancer progression that will lead to the discovery of new, more tailored and personalized anticancer therapies. One of the largest group of enzymes that greatly contribute in cancer progression are proteases. In this project I will leverage the production of highly selective chemical probes to investigate the contribution of medically important proteases in tumor progression in PDX (Patient-Derived Xenograft) mice models using a new analytical technique - mass cytometry. This goal will be achieved via a four-step approach employing techniques from organic chemistry, analytical chemistry, biochemistry and biology making this project multidisciplinary. Proteases that have been chosen for this purpose are caspases, legumain and cathepsins B, L and S for which I will synthesize very specific, small molecule radiolabeled inhibitors suitable for mass cytometry approach. These probes will be first evaluated on recombinant enzymes and simple cell systems and then they will be applied to PDX mice studies. PDX models offer an excellent possibility to study human cancer biology in system most closely related to in vivo pathology. So far there are no reports in the literature regarding the use of mass cytometry in studies of PDX mice models, which makes this project very unique and innovative. This PROVIST project will be performed in Sanford Burnham Medical Research Institute, USA (24-months outgoing phase, prof. Guy Salvesen Lab) and at Wroclaw University of Technology, Poland (12-months return phase, dr. Marcin Drag Lab). The research and training profile of these units fits all the objectives that are included into PROVIST project (scientific research and personal career development).

Breast cancer (BC) accounts for 28 % of the total cancer cases in the European Union (EU) and is the leading cause of cancer-related mortality of European women. The stratification of individual BC sub-types for corresponding therapy modalities is poor. Therapy outcomes in several BC sub-types are unsatisfactory. Its diagnosis is marred by high proportion of false positives and the economic burden to healthcare systems is very high. To overcome this NANOCARGO will develop a simultaneous diagnosis and therapy (theranostics) approach based on a multimodal nanocomposite termed as nanocargos. The battle against cancer is much more effectively fought if it is aided by early detection and, potentially concurrent, efficient treatment. NANOCARGO, introduces a new paradigm that theranostics can be made far more effective if a multimodal action can be integrated by adding a plasmonic shell to a magnetic nanoparticle core. The plasmonic shell can be functionalized with the chemotherapeutic drugs and aptamars. Magnetic@gold and magnetic@silver type core/shell nanocargos can be conjugated with anticancer aptamer. These nanocargos can be stimulated by simultaneous application of magnetic hyperthermia and photonic therapy. Cellular delivery can benefit from photoporation. Anticancer therapy can thus be made much more effective through the multimodal actions of these nanocargos exposed to endo-luminal, minimally invasive optical stimulation and extra-corporeal magnetic resonance imaging based excitation. Such a combined will maximise the delivery of these nanocargos into tumor cells. The magnetic core is advantageous for a controlled delivery of aptamer through an externally applied magnetic field. Gold and silver shell will support aptamer attachment. X-ray computed Tomography (CT) imaging contrast of absorbing tumors will be better due to higher X-ray absorption of gold and silver.

The goal of this project is to design a new Erasmus Mundus Master program focused on industrial applications of numerical methods. During the project duration, a new consortium will be established. The HEIs of the future consortium will prepare an innovative and integrated program, based on a jointly developed curriculum and composed of lectures fully recognized by all consortium partners. The Master program profile will emphasize scientific, technical and engineering challenges related to advanced industrial support by numerical modeling and simulations. The courses will address both the fundamentals and the integration of the natural science (chemistry, physics) into engineering problem solving. The Master program will be tailored to provide flexibility in applications of numerical tools. The graduate engineers will be experts in numerical modeling methodology and will be able to work in a broad spectrum of industries. This project will prepare a new application of the Erasmus Mundus Joint Master (EMJM) project which will offer a fully integrated curriculum delivered by partners from HEIs and industry. The new Master will aim at recruiting excellent students worldwide and will include compulsory physical mobility for all recruited students. The curriculum will constitute a four-semester program in Engineering. The coordinating Institution of the new EMJM program will be The Wroclaw University of Science and Technology (Politechnika Wroclawska, Wroclaw, Poland). Two European Universities (Sofia University, Sofia, Bulgaria and University of Montpellier, Montpellier, France) and two Partner Countries Universities (Queensland University, from Australia and Rutgers University, from USA) have agreed to participate in this project and work together on the new EMJM proposal.