Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - MOGLYNET (Modulation of glycolytic flux as a new approach for treatment of atherosclerosis and plaque stabilization: a multidisciplinary study)

Teaser

The mission of Moglynet is to define a joint doctorate educational training model in Drug Discovery and Development where Academia and Industry, supported by other institutions/organizations, join their forces to create a common knowledge and language for those working in the...

Summary

The mission of Moglynet is to define a joint doctorate educational training model in Drug Discovery and Development where Academia and Industry, supported by other institutions/organizations, join their forces to create a common knowledge and language for those working in the Pharma-field.

The Moglynet scientific activity focuses on atherosclerotic cardiovascular disease, a disease of aging that is the major cause of death in the western world. Thanks to cholesterol-lowering drugs, the lifespan and wellbeing of patients have been significantly improved. However, a large group of patients does not fully benefit from current pharmacological intervention. A relatively new aspect in the search for strategies to tackle atherosclerosis, preventing rupture of atherosclerotic plaques and myocardial infarctions, is the role of angiogenesis in the plaques. Our aim is to control the neovessel formation in the atherogenic process.
To reach this goal, a multidisciplinary consortium was created, pulling together researchers experienced in drug discovery and development (drug design, synthesis of new molecules, cell metabolism, angiogenesis, cardiovascular diseases and imaging technologies). We are working synergistically to design and develop new compounds modulating a new enzymatic target.
In this way, progression of atherosclerotic plaque growth and rupture of plaques may be prevented, and consequently the occurrence of acute cardiovascular events such as myocardial infarctions and strokes may be reduced

This research program is unique as compared to the traditional PhD research programmes at the different partner universities, where each graduate student has an individual research project, unrelated to the project of the other fellows. The multidisciplinary context of the proposed doctorate provides our 12 Early Stage Researchers (ESRs) a holistic view on different research approaches to the same core.
Seven industrial partners are part of the Consortium. The contribution of non-academic sector is of fundamental importance in supporting academia. By the way of the secondment activity in Industry, the entrepreneurial culture of our ESRs is strengthened and complemented.

Work performed

The work of the Moglynet Consortium is addressed to two main objectives focused on i) the scientific and ii) the training programme.

The scientific project is structured into three work packages (WPs), corresponding to the different objectives.
The first two WPs are addressed to the inhibition of glycolysis that represents an attractive therapeutic approach to reduce pathological neovascularization and to delay the progression of plaque or induce regression, controlling excessive inflammation and improper immune response.
Libraries of small molecules and peptides were designed using virtual screening and computational alanine scanning (CAS), respectively.
Some molecules were selected and synthesized. Different in vitro assays were performed and some molecules were selected for their ability to bind our enzymatic target and to inhibit the proliferation/migration of different EC lines.

The third WP is focused on the investigation of the potential role of modulators, and other glycolytic pathway flux key players, in endothelial dysfunctionality associated to comorbidities in patients with atherosclerosis.

Training activity. One of the main aims of the Moglynet programme is to create a common knowledge and language for those working in the field of drugs design and development. ESRs tend to have a specialised background restricted to a single discipline, whereas the MOGLYNET project is highly multidisciplinary. Aiming to cover this gap, the Moglynet Consortium organized different activities, i.e. courses with different scientific topics related to the project, workshops with practical session on specific skills and the first summer school on PET imaging. Advanced courses on specific topics are delivered at the six Doctoral Courses/Schools of the five beneficiary institutions.
Each ESR has his/her Individual Research Project. Joint monitoring and evaluation for each student is ensured by two beneficiaries and the industrial partner supervisors.
As stated in the Moglynet programme, the Supervisory Board recognised the first year ECTS to each ESR according to the corresponding activities.

Management. All the objectives defined in the Moglynet project were achieved according to the deliverables and milestones. All committees were appointed at the Kick-off meeting.
Principles of the Moglynet Recruitment Procedure were defined in the kick-of-meeting where a central selection was planned. 12 ESRs were regularly enrolled.
The agreement on Joint supervision leading to a double degree PhD award was signed by all Beneficiaries involved in the Moglynet programme

Dissemination Activity. In these two years the Consortium paved the way to establish fruitful communication and dissemination strategy of the Moglynet activities. The Moglynet Brochure was produced and uploaded on the Moglynet web-site, created at the beginning of the project.
All ESRs have already presented their scientific results at conferences/workshops in the form of posters or oral communications. Two of them received an award for their posters. Three scientific publications were also delivered.

Final results

The primary aim of Moglynet is to expose ESRs to bridging training and work practices with a focus on the development of critical Pharma-skills. In particular, the Moglynet programme exposes recruited researchers to a multidisciplinary and inter-sectorial environment, making researcher careers more attractive via cooperation between academia/companies. The non-academic contribution provides the way forward to help academia in meeting the educational needs of industry.
Using this model, our objective is to provide the academic community with a new cooperative PhD training programme model on Drug Discovery and Development that may be adopted independently from the research topic.
The Consortium wishes to promote communication between the scientific community and the general public. To reach these objectives a strong involvement of ESRs has been already put in action. ESRs are responsible for maintaining the project’s webpage, and for exploiting the communication potential of social networks. Workshops for undergraduate students and for students of secondary schools were organized with active ESRs participation. Flyers and Brochure informing on the Project and of important events (Summer School, workshops and so on... ) were prepared and distributed with the collaboration of all the participants to the Network. Articles in non-specialized press were published or are in preparation.

Website & more info

More info: http://www.moglynet.com/website/.