To investigate normal and deregulated systems and pathways that characterize the pathology of serious diseases and genetic disorders.
The Molecular Biomedicine and Technology (MBT) area focus on the study of the properties and interactions of biomedically relevant molecules, and on the design and development of novel biomolecular devices. In general terms, the MBT integrates molecular engineering and biophysical characterization to develop better systems for detection, diagnostics, and delivery of pharmaceuticals.
One of the characteristics of this thematic area is that the MBT produces the needed biomolecules for the systems under study. The MBT has extensive expertise as well as the required technology for production and purification of such biomolecules, in particular large-scale protein expression, purification and analysis followed by the biophysical characterization of proteins and lipids.
MBT main research lines
Development and characterization of novel polymeric drug delivery systems
Polymers of either natural or synthetic origin are used to produce vehicles for the delivery of molecules of interest, for example proteins, antigens, genetic material (DNA, siRNA) and low molecular weight drugs that face delivery limitations. Particular focus within the MBT is directed towards systems that address the treatment of pulmonary diseases, such as tuberculosis and cystic fibrosis, and the ocular delivery of gene expressing systems targeting the retinal area.
Dynamics and structure of membranes
The MBT is also examining biomembrane structure, organization and dynamics comprising the influence of key components such as cholesterol, known to be involved in many clinically important pathologies. Understanding how protein and solutes partition into lipid bilayers is also of interest within the MBT due to its relevance to membrane properties and function.
Protein nanoparticles for molecular therapy
Protein nanoparticles are developed within the MBT for the targeted delivery of proteins to treat disease. Based on the full virus genome the MBT focuses on the selection and optimization of gene constructs responsible for nanoparticle assembly. These nanoparticles are further engineered within the MBT to incorporate scFvs and single domain recombinant antibodies as therapeutic motifs and to present specific target motifs at their surface. We develop such systems in order to generate nanodelivery systems suitable for further manipulation and for targeted molecular delivery in most relevant disease settings, in particular HIV1.
Development of biosensor technology driven to biomedical applications
New scientific instruments and techniques including acoustic, optical and microelectronic transducers are developed within the MBT for the study of biomedical relevant interactions. This includes HIV antigens and single chain antibodies that are integrated with engineering principles and concepts enabling the MBT to design novel biosensing devices. Biosensors are also being developed to assess the mechanism of cell adhesion and differentiation. Based on the propagation of acoustic waves, the MBT has developed models that describes the biosensor signal as a response to the morphological alteration of the cell during adhesion. Such sensors are being developed for detection of the effect of drugs and also to optimize and evaluate the effect of differentiation factors The MBT is also screening of transcription factors using biosensors, addressing protein-DNA interactions and conformational changes. A prototype technique integrating an acoustic sensor and a flow calorimeter (QCMHCC) is being developed within the MBT for the rapid and complete thermodynamic characterization of biomolecular interactions, aimed at various applications in biomedicine, in particular drug screening/design.
Protein folding in human disease
Protein folding is crucial to the study of human disease that arises from protein misfolding, the storage and use of therapeutic proteins to treat disease, the development of novel protein delivery systems and the application of proteins as bio-sensors. The study of oxidative protein folding in the endoplasmic reticulum is particularly important within neurological disorders. Studies of protein folding, stability and misfolding are conducted for several proteins, including the prion protein involved in prion diseases, haemoglobin, oxidoredutases, and small model proteins such as bovine serum albumin.
Molecular Modelling and Simulation
The MBT also incorporates computational and bioinformatics studies that significantly support, complement and allow the in-depth analysis of our on-going projects. Particular focus within the MBT has been the examination of in-silico protein-protein interactions, ligand-protein docking studies and relevance of protein electrostatics to protein structure and function.