MOLECULAR IMAGING: MOLECULAR SIGNATURE OF HAEMATIC CELLS BY BIOPHOTONIC MICROSCOPY

The main goal of BiophotOmics project is to develop an innovative portable medical device (HS-Bio), for the molecular imaging of circulating haematic cells plasmatic membranes, with a particular focus of on the membrane of red blood cells (RBCs), as an innovative molecular sensor of health status in patients. We want to identify new diagnostic and predictive markers of the health status, by combining Key Enabling Technologies (KET) to a “-omic” approach. Whole blood is the main character of this project, as starting from the analysis of a single blood drop, we want to characterize the membrane plasmatic molecules, in particular the fatty acids, as the principal component of membrane phospholipids and comprehend how the phospholipid content may be different in health and pathologic status. These differences will be, therefore, related to clinic parameters, to finally generate standards that can be used to discriminate among different diseases.

INNOVATIVE ANALYSIS OF MEMBRANE COMPOUNDS

STUDY OF DISEASES:

BiophotOmics project is focused on the analysis of membrane molecules, such as lipids, in metabolic disease (diabetes, gout, hypercholesterolemia, obesity), neurologic diseases (Alzheimer’s disease, Multiple Sclerosis disease), and tumor disease (Hepato Cellular Carcinoma - HCC).

METABOLIC DISEASES

Metabolic diseases consist of metabolic pathway alterations, such as diabetes, hyperglycemia, hipoglycemia, and obesity.

NEUROLOGIC DISEASES

Neurologic diseases include all disorders related to the central nervous system, such as Multiple Sclerosis diseases, cerebrovascular disease, Alzheimer’s and Parkinson’s disease, epylessia, and peripheral nervous system, such as myasthenia.

TUMOUR DISEASES

Tumor diseases are characterized by uncontrolled cell proliferation, so that they become capable to do self-renewal, neo-angiogenesis escaping the immune system, becoming also able in infiltrating into normal tissues and, therefore, compromising structures and functions.

IN VITRO EXPERIMENTS

The aim of in vitro experiments is to find a possible correlation between lipidomic of plasma membrane of red blood cell and nervous and glial cells in basal conditions and after stimuli that mimic the animal disease models previously described (i.e. inflammation, iperglycemia and exposure to beta-amiloid peptides). Macrophages (cell line), neurons, astrocytes and oligodendrocytes (primary cell cultures) are the cells included in the study.

From PRE-CLINICAL RESEARCH

EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
MULTIPLE SCLEROSIS (EAE)

The experimental disease is characterized by inflammation, strong demyelination and partial re-myelination. Pathology progression is daily monitored from induction (active immunization) assigning a neurological disability score at each mouse. The disease reaches the severity peak two weeks after induction (acute phase), then the animals goes to a partial remission and chronicization (remission phase). Body weight gain of EAE mice is reduced compared to the control animal.

MURINE DIABETES TYPE

Dbdb mouse carries a spontaneous mutation in the gene that encodes for the Leptin Receptor. These animals show severe obesity, Hyperglycemia, polydipsia, polyuria. This model shows altered phenotype in metabolic, reproductive and immune systems, making this model coherent with human type 2 diabetes.

Tg2576 – ALZHEIMER’S DISEASE

Many animal models for this dementia are available. The transgenic model we choose (Tg2576), carries the Swedish mutation of the gene encoding for amyloid precurson protein (APP). Early signs of cognitive impairment appear in 5/6 months old mice. The animals are monitored since adulthood with behavioral test, i.e. Y-maze (showed in the pictures below), to evaluate learning and different memories.

HEPATOCELLULAR CARCINOMA MOUSE MODEL (HCC)

Hepatocellular carcinoma is a multistep pathologic process, characterized by the progressive evolution of hepatic diseases, causing cellular degeneration driven by fibrosis and cirrhosis, to the necrosis and tumor development.
In hepatocellular carcinoma mouse model, mice are treated with an intraperitoneal injection of Dietyl-nitrosammina (DEN) followed by be-weekly treatment with carbonate Tetrachloride (CCL4), in order to study all the different steps related to the tumor process.

to CLINICAL RESEARCH

Clinical research is performed on human patients, to acquire more knowledge related to the diseases and to find out new treatments, and to develop new devices and new diagnostic procedures, for improving health care. Therefore, volunteers and patients affected with metabolic, neurologic, and tumor diseases will be recruited allowing us to perform more advanced studies.