POST-DOCTORAL FELLOWSHIP – TYPE A, 2022 II° CALL
Second call for post-doc type A fellowship 2022 published on 23/12/2022, dead line for submission 30/01/2023 at noon (Italian time) at the BIOMETRA Department
Research lines suggested by the Department within the areas:
1. Endocrine and methabolic pathologies
2. Chemistry and physics of biomolecules and cellular biophysics
1a) Giovanni Vitale
Dissecting the cross-talk between adipose tissue and neuroendocrine tumors.
The teleost zebrafish (Danio rerio) is a reliable and versatile experimental model for many human pathological conditions, including obesity. Zebrafish is also an excellent experimental model for vascular biology studies. The embryo transparency, together with the availability of transgenic lines that express fluorescent molecules in different cell populations, allow to follow the vascular development in vivo. Moreover, zebrafish embryos and larvae have been widely used as recipients for tumor xenograft experiments with human and murine tumor cells in order to study the tumor-induced angiogenesis.
The aims of the present study are:
- To develop a new experimental model based on the xenograft in zebrafish embryos of adipose cells derived from the subcutaneous and visceral compartment of obese patients.
- To study the reciprocal influence of adipose cells and neuroendocrine tumors on cell proliferation, migration and tumor-induced angiogenesis.
Study and molecular characterization of gonadal dysfunction in patients with diabetes mellitus.
Diabetes mellitus (DM) is a disease with a high social impact that affects over 530 million people between the ages of 20 and 79 worldwide (International Diabetes Federation data from 2021). It is known that DM can determine chronic complications affecting various organs and tissues. Among the possible associated conditions is also the dysfunction of the hypothalamic-pituitary-gonadal axis, although the pathophysiological basis of this association is currently poorly understood.
This research project aims to:
- Evaluate the real prevalence of hypothalamic-pituitary-gonadal axis (HPG) dysfunction in patients with DM
- Evaluate the possible correlation between hormonal impairments and individual predisposing characteristics investigated through molecular characterization (genetic predisposition to HPG axis fragility and/or peripheral receptor sensitivity)
- Investigate possible associations between prevalence and severity of gonadal hormone defect and obesity/metabolic syndrome, dysfunction of other endocrine axes, possible etiopathogenetic mechanisms, onset of DM complications and current therapy.
1c) Enzo Nisoli
Nutritional and pharmacological interventions that modify the gut microbiota and prevent obesity-related non-alcoholic fatty liver disease (NAFLD) and depression: preclinical and clinical approaches.
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition correlated to the rise of obesity that predisposes to severe complications. Approved drugs are lacking; thus, diet and physical activity are the only recommended therapeutic options. Atypical depression is also frequent in NAFLD patients. A possible explanation is the involvement of the microbiota-gut-brain axis, a bidirectional network linking the central and enteric nervous systems. Further, mitochondrial dysfunction and oxidative stress participate in NAFLD and depression pathogenesis.
The aims of the present study are to:
- Use a well-known mouse NAFLD model (high-fat, high-sugar diet feeding) to explore NAFLD score, changes in liver mitochondrial function, and anxiety and depression-related behavioural changes.
- Investigate the effects of novel drugs and/or metabolic modulators able to modulate liver and brain mitochondrial activity and favour changes in the gut microbiota.
- Translate novel therapeutic approaches into clinical trials.
Self-assembly, liquid-liquid phase transition and non-enzymatic polymerization in solutions of activated mono and oligo-nucleotides. Besides their key role in genic transmission and regulation, nucleic acids have been found to exhibit a unique capacity of supramolecular structuring, resulting from the various intermolecular interactions they are capable of. Such structures are driven by sequence hybridization, as in the case of the so called DNA nanotechnology, or by base stacking interactions, as in the case of the formation of liquid crystal ordering.
In this project we aim at studying phase transitions, supramolecular structures, and chemical reactivity in liquid crystal phases of mono and oligonucleotides in solution. The focus will be set on important aspects in the development of new synthetic and cathalytic processes and in the formulation of new scenarios of prebiotic chemistry. Specifically we aim at:
- synthesizing activated derivatives of nucleic acids with mesogenic properties and studying their reactivity inside liquid crystalline phases;
- studying liquid-liquid crystal phase transitions in mixtures of nucleic acids and polycations;
- studying interactions between liquid crystalline phases of nucleic acids and structured and functionalized surfaces.
Viscoelasticity, plasticity, and stress-induced structural remodeling in model extracellular matrices.
The extracellular matrix (ECM) plays a key regulatory role in a wide spectrum of biological mechanisms, in particular in cancer development and invasion. Besides providing biochemical stimuli to the tumour mass and modulating the immune response, the ECM plays an important role of mechanical constraint, whose effectiveness critically depends on its rheological properties. Understanding the complex interplay among the ECM mechanical response, cell-generated stresses and collective cancer invasion is one of the big challenges at the interface of physics, material science and cancer biology.
The project tackles this topic in two steps of increasing complexity. The first part will be devoted to the quantitative study of the mechanical response of various model ECM, through optical rheo-microscopy and active microrheology. In particular, the effects of controlled mechanical stresses on irreversible modifications of the microstructure will be investigated. In the second part, 3D traction force microscopy experiments (a non-invasive technique which can evaluate the forces exerted by the cells on a substrate) will be performed on tumour cell spheroids encapsulated in the previously characterized matrices. The quantitative analysis of the experiments will allow to simultaneously measure cell motility and structural/functional alterations in ECM and to investigate their causal correlations.