A detail of the enzyme activity filtration process (C-P lyase enzyme) on Agilent cartridges
A cell can be regarded as the ultimate example of a complex dynamical system. The internal composition of the cell needs to be finely regulated to establish the occurrence of fundamental biophysical processes. Cellular membranes, their pores and channels regulates flows of molecules and ions into and out of cells and cell compartments.
The focus of this research activity is to understand how the transport mechanism are able to maintain the cellular homeostasis and to play a pivotal role in the communication between cells.
Transport across membranes
One of the main research topics of the institute is the study of the channels, transporters and receptors involved in ion transport through biological membranes, in order to understand the molecular mechanisms responsible for the regulation of numerous cellular functions, such as cellular homoeostasis and communication between cells.
We study the structure-function correlation of transport mechanisms through the expression of DNA (or RNA) with point mutations. The functional experiments are carried out in appropriately transfected cell lines, and in frog oocytes injected with the RNA that expresses the protein of interest. Measurements are made with electrophysiological techniques (patch-clamp or voltage clamp), by fluorescence measurements with ion-sensitive probes and with ion-sensitive electrodes. The observations are complemented with biochemical methods.
Principal Investigators: Michael Pusch − Alessandra Picollo − Daniele Arosio − Anna Boccaccio – Cristiana Picco
Cell physiology
We study the role of the control of intracellular calcium homeostasis and of the channels responsible for the control of cell volume in the mechanisms of control of cell proliferation and apoptosis.
Principal Investigators: Michael Pusch − Alessandra Picollo − Carla Marchetti – Debora Baroni
Pathophysiology of genetic diseases
Understanding the molecular pathophysiology of many inherited diseases allows the design of diagnostic and therapeutic strategies and prognosis for the disease. We analyze the characteristics of the proteins responsible for various genetic diseases, both in cell cultures from patients, and through the heterologous expression of the appropriately modified protein. The results are supported by molecular models and bioinformatics studies.
Among the genetic diseases that are the object of our interest are those produced by mutations of the chloride channel of the CLC family (myotonia congenita, Bartter’s disease Dent’s disease, ostopetrosis-ClC-7, leukoenphalopathies and cognitive disability), cystic fibrosis, genetic diseases associated to TMEM16/anoctamin protein familiy (muscular dystrophy, ataxia, gnatodiaphyseal dysplasia, dystonia), mutations sodium channel (familial hemiplegic type 3 migraine, generalized epilepsy, Dravet syndrome), Spinal and Bulbar Muscular Atrophy (SBMA), Spinal Muscular Atrophy (SMA), AGel amyloidosis and Familial Encephalopathy with Neuroserpin Inclusion Bodies.
Principal Investigators: Anna Elisabetta Boccaccio – Michael Pusch − Alessandra Picollo − Oscar Moran − Carlo Musio − Paola Gavazzo − Federica Viti − Mauro Dalla Serra − Gabiella Viero − Michela Bollati − Mauro Manno − Debora Baroni
Molecular Pharmacology
Pharmacological research ranges from the discovery of new drugs, by screening compounds in vitro or in silico, to the understanding of molecular mechanisms of action of drugs. We apply functional, biochemical and toxicological methods, structural biology and computer molecular models.
The main targets are CFTR modulators for cystic fibrosis, the development of antiviral agents, substances that alter proliferation and apoptosis in tumor cells, and the neurotoxin mechanism. A new line explores the possibilities of the CRISPR / Cas9 technique to edit defective DNA in cystic fibrosis.
Principal Investigators: Michael Pusch − Debora Baroni − Oscar Moran − Michele Fiore − Daniele Arosio − Eloise Mastrangelo − Mario Milani – Michael Whalen