Development of advances protease inhibitor nanoformulations for human disease

 

Outline, including interdisciplinary dimension

This project will bring together nanotechnology, medicinal chemistry and human biology in a unique project to develop optimal formulations for the delivery of protease inhibitors.  There is an increasing understanding of the role of cysteine cathepsin proteases in the development of cancer and immunity, based on clinical observations, cell biological and murine models.  However, the field is currently frustrated by the inability to exploit these targets and translate cathepsin inhibitors to the clinic.  This is a consequence of compounds developed to date having insufficient pharmacokinetic and pharmacodynamic properties.  New compounds and new formulations are needed and this will be the focus of this present project. These research disciplines are distinctly different, requiring the development of a broad range of expertises and requiring supervisors from each of these specialisms.

Key words/descriptors

cathepsin, nanomedicine, inhibitor

First supervisor

Professor Chris Scott - School of Pharmacy

Secondary supervisor from a complementary discipline

Dr Rich Williams - The Patrick G Johnston Centre for Cancer Research

Professor Brice Korkmaz - Centre d'Etude des Pathologies Respiratoires

Supervisors’ track record of PhD completions, plus excellence and international standing in the project area

19 students completed PhD to date.  Prof Scott is an acknowledged expert in the international community in cathepsin biology research (e.g. 2 Gordon Research Symposia talks in last four years and session chair).  He is also well known in the field of nanomedicine, currently funded by MRC and NIH to develop new nanomedicine for the treatment of cancer and other conditions.

Intersectoral exposure and/or international mobility

(e.g. secondments to/collaboration with partner organizations)

Opportunity to travel to leading laboratory in France, as well as connect to other leading European academic laboratories in Slovenia and Germany.

Describe briefly the international profile of the partner

Dr Brice Korkmaz.  An internationally recognised expert in the study of protease activity in human lung diseases, such as Cathepin S, Cathepsin C and Neurophil Elastase. We recently published work together on the study of Cathepsin C activation in Neutrophils via Cathepsin S.

Training that will be provided through the research project itself

Scott lab-training in cathepsin biology and nanotechnology drug formulation (combination of both pharmaceutics and cell biology). Williams lab: training in medicinal chemistry and computational modelling. Korkmaz lab: delivery of Nanoparticle encapsulated inhibitors in models of lung disease.

Examples of additional training in non-research transferable skills

Training will be provided in entrepreneurship; communications training; team building and general leadership.

Expected dissemination of results: peer-reviewed journals, seminars, workshop and conferences at European/international level

(e.g. public talks, visits to schools, open days, QUB impact showcase)

We anticipate that in line with students that each of the supervisors have had before that the student will present oral and poster presentations at the Gordon Research Symposia (Italy), Tiers Winter School in Proteases (Italy, all students are given oral presentation opportunity), International Proteolysis Society (international locations every two years - 2017 is in Banff for example).

Expected impact activities

(e.g. public talks, visits to schools, open days, QUB impact showcase)

The Scott group works closely with patient groups such as the NI Brainwaves organisation (brain cancer) as well as science week in local schools across Northern Ireland.  Scott has already taken part in the Impact showcase in the past and is involved each year as DR for School of Pharmacy.