Coordination: Manuel Prieto and Miguel Castanho

 

 

Objectives

 

It is the purpose of this course to introduce the concepts of the interrelated subjects of drug delivery and cell mimics.

 

Drug Delivery

 

Synthetic systems are used to transfer a drug to a specific biological target, maximizing its efficiency. This strongly depends on the specific physico-chemical properties of the system, and on its interaction with the drug. The students will learn about the different types of systems, as well as their advantages/disadvantages.

 

Cell Mimics

 

The complexity of the cell prevents direct qualitative/quantitative conclusions about the structural and dynamical information that is recovered from direct studies at the cell level. In this way, students will learn about approaches of increasing complexity using model systems of membranes, since in this case it is possible to carefully manipulate the system composition (both lipids and proteins), and e.g., establish in a controlled situation the response of reporter molecules (probes), that are essential in relevant spectroscopies and in the microscopy methodologies. Also, model systems are the starting point in the development of the artificial cell. Lipids are assembled with polymers (polymersomes), and this supramolecular entity is the starting point of the so-called “minimal cell”.

 

Program

 

1- Basic concepts of model systems of biological bilayers.
2- Membrane biophysics, lipid phases, cholesterol-lipid interaction, lipid rafts.
3- Drug delivery methodologies. Interaction with lipid bilayers mimicking cell membranes and supported confluent cells as a model for the brain-blood barrier. Lipid-water partition coefficients and membrane permeation.
4- Lipid-protein interaction in model systems and cells. Quantification of the interaction.
5- Advanced microscopy methodologies for imaging, structural (FRET, FLIM) and dynamic information (FCS, FRAP). Application to model systems (Giant Unilamellar Vesicles) and cells. Theory and demonstrations.
6- Cell studies and advanced microscopy: endocytosis and intracellular traffic.
7- Case studies: i) apoptosis and ceramide domains, ii) PIP2 lateral organization in living cells, iii) enzymatic processes under the microscope, iv) amyloid fiber formation, v) physiological targets of cytoprotective/cytotoxic bile acids in both hepatic and non-hepatic cells, vi) infection by HIV-1 mediated by the gp120-gp41 viral glycoproteins complex.
8- Advanced cell mimics systems- “polymersomes”.

 

Evaluation Methodology

 

In the end of the first week, the PhD students will make an individual presentation (20 min plus 10 min discussion), about a subject that is either chosen by them (in this case it should be approved by the teaching staff), or suggested by the faculty members. This presentation should describe the basis of the methodology that is used in the work, as well as a critical discussions of the results. Also, each student will lead the discussion about a presentation of a colleague, and this one should be centered on a different subject (50%).

 

In the end of the second week, the students will write a short essay dealing with a problem suggested by the faculty members, and describing how to address it on the basis of the methodologies that were learned in the course. (50%).