Translational Medicine

Dottorati
Doctoral programme (PhD)
A.Y. 2021/2022
Study area
Medicine and Healthcare
Doctoral programme (PhD)
3
Years
Dipartimento di Scienze biomediche per la salute - Via Mangiagalli, 31 - 20133 Milano
English
PhD Coordinator
The doctoral programme aims to train researchers who are able to develop research projects that bridge the gap between laboratory activity and clinical sciences, facilitating the translational process in both directions.
Aims:
1. understand and study biological structures in the different levels of organisation, their physiological and pathological modifications in the framework of interactions between people and the environment, exploring diagnostic and therapeutic interventions and facilitating their application in clinical practice;
2. learn a scientific translational research approach which can favour points of contact between biological and clinical-behavioural discoveries and preventive, therapeutic and rehabilitation practices in order to improve di health and lifestyle, also considering the global increase in life expectancy;
3. acquire a solid preparation in the methodological disciplines required to formulate correct experimental hypotheses, define experimental designs and critically interpret results;
4. promote communication between biological and clinical-behavioural research, particularly in relation to movement and physical activity in the area of prevention, mental-physical wellbeing, sport and professional performance, in conditions of health, illness and disability, in a unified perspective;
5. understand the ethical implications of clinical and biological research.
Tutte le classi di laurea magistrale - All classes of master's degree
Dipartimento di Scienze biomediche per la salute - Via Mangiagalli, 31 - 20133 Milano
Title Professor(s)
The research line “Cardiopulmonary interactions in heart failure” of the PhD in Translational Medicine aims to design and develop translational research projects that, starting from the systemic pathology of heart failure, analyze the complex pathophysiological relationships that exist between the heart and lung, with particular reference to the cardiopulmonary response to exercise and the use of diagnostic and prognostic biomarkers.
Requirements: The candidate must demonstrate interest and continuity in conducting research projects in the field of heart failure and cardiopulmonary pathophysiology. They must also have an aptitude for work (personal and in teams) in the procedures of project design, patient enrolment, experimental procedures, and analysis of collected data for the drafting of scientific papers. Medical and/or laboratory skills.
GBA and Parkinson’s Disease: Mutations in GBA gene, an enzyme involved in the sphingolipid catabolism, are a major risk factor for Parkinson’s disease (PD). The proposed research project is aimed to dissect the molecular mechanism responsible for the onset of neurodegeneration upon GBA loss of function. In addition, it will be investigated the possible rescue effect of small molecules able to enhance GBA activity and/or to reduce the production of the uncatabolized substrate.
Requirements: Cell culture, lipid analysis, enzymatic assays
Lipid-based therapeutic strategies to optimize the effectiveness of innovative drugs to rescue mutated CFTR: One of the main obstacles in the functional recovery of CFTR lies in the poor stability of the mutated protein on the cell membrane. The project aims to investigate the possibility that exogenous administration of lipids, which are deficient in CF bronchial epithelial cells, may help the functional recovery of CFTR.
Requirements: Cell culture, lipid analysis, enzymatic assays
Role of ion channels mutations assocaited with cardiac electrical dysfunctions
Requirements: Specific knowledge in electrophysiological techniques to record currents in singel cells. Competences in the biomolecular methodologies (DNA transfection and cell culture).
Role of the AMPK protein as a crucial modulator of ion channels' functions associated with the ageing process
Requirements: Specific knowledge in electrophysiological techniques to record currents in singel cells. Competences in the biomolecular methodologies (DNA transfection and cell culture).
Innate immunity in malaria-leishmaniasis co-infection. Malaria and leishmaniasis are severe parasitic diseases endemic in the tropics. The two infections can co-occur and cross-interact in the same patient with implications on the course of the two diseases. The aim of the project is to investigate the role of malaria and leishmania co-infection on macrophages and dendritic cell functions. Expression of co-stimulatory molecules, cytokines release and inflammasome activation will be investigated.
Requirements: Basic knowledge in cell culture and in molecular biology
Characterization of molecular mechanisms involved in antigen presentation pathway responsible for antiviral immune response (HIV and SARS-CoV-2) through characterization of: 1. ERAP1 and ERAP2 gene polymorphisms 2. innate and acquired immune response triggered by different ERAPs variants 3. ERAPs gene variants in susceptibility to viral infections through in vitro infection assay (BSL3) and gene expression analyses (RNAseq); 4. ERAP1 and ERAP2 specific inhibitors 5. ERAPs-specific miRNAs
Requirements: Knowledge of cellular and molecular immunology with omics approach.
The project will focus on next-generation sequencing (NGS) approaches on monoclonal gammopathy of unknown significance (MGUS), smouldering multiple myeloma (SMM) and active multiple myeloma (MM). In asymptomatic cases, we will study initiating lesions and those arising later, associated with disease progression. In active MM, we will develop an NGS-based diagnostic test for the extended genotyping of cases, developing new prognostic tests and identifying new potential therapeutic targets.
Requirements: Candidates will have experience handling primary humans blood samples, cell separation, DNA-RNA extraction, cellular and molecular biology protocols.
Machine learning in psychiatric neurosciences: using clinical neuroimaging and cognitive data to ameliorate diagnosis, treatment response and outcome prediction for major psychiatric disorders
Requirements: Some knowledge in creating database and handling clinical, neuroimaging and cognitive data. Some experience in utilizing softwares such as Matlab, SPSS or R
Biomarkers associated with the diagnosis of Mood Disorders: epigenetic, inflammatory and hormonal factors involved in the etiology and outcome of Mood Disorders
Requirements: Competence in the field of translational research (including mental health assessment) and/or in the field of molecular biology
The project will address genetic, molecular and cellular aspects linked to the pathogenesis of serpinopathies, a class of conformational diseases do to serpins mutations. Serpins are a superfamily of proteins involved in diverse physiological processes, ranging from blood coagulation, fibrinolysis, inflammation to immunity. Their peculiar mechanism of action renders serpins particularly vulnerable to point mutations, that often lead to both a gain and loss of function and finally to disease.
Requirements: Basic knowledge of biochemistry, cellular and molecular biology.
The project is focused on the endocannabinoid system, a complex network composed of receptors, their ligands, and enzymes regulating the synthesis, release, uptake, and degradation of the signaling transmitters, that is widely distributed in both the central nervous system and peripheral tissues. This signaling system plays a crucial role in regulating a wide range of physiological and pathological processes, thus its modulation can open fascinating therapeutic opportunities for the treatment of a variety of diseases
Requirements: Basic knowledge of biochemistry, cellular and molecular biology.
On the route to the construction of safe-stimuli responsive ion-channel proteins: structural interference between channel and hosting membrane. Ion channels require to be held by a membrane. Within a wider program connected to an ERC project (noMAGIC), aimed at the construction of potassium channel variants capable of responding to external safe stimuli, the structural aspects of membrane-protein interaction will be followed with advanced spectroscopic techniques. The activity will be done both at the BIOMETRA Dept. (UNIMI) and at the international Large-Scale-Facilities located in Europe, in collaboration with electrophysiology groups in Milano and in Darmstadt.
Requirements: Good knowledge in physics or biology. Some skill in scattering techniques is preferred.
Molecular basis of neurodegenerative diseases. The aim is the study of the structural features and interaction properties of proteins involved, in their native or mutated form, in basic processes of degenerative diseases affecting the nervous system, either central or peripheric, like abeta (AD), tau (tauopathies), TDP43 (SLA). The activity will be done both at the BIOMETRA Dept. (UNIMI) and at the international European Large-Scale-Facilities, in collaboration with the Mario Negri Institute.
Requirements: Good knowledge in physics or biology. Some skill in scattering techniques is preferred.
The accumulation of genetic mutations in the intestinal epithelial cells and a local procarcinogenic immune response drive the adenoma-to-colorectal carcinoma (CRC) sequence. Although intestinal bacteria are involved, how alterations of the gut microbiota composition (i.e. dysbiosis) contribute to this process is poorly defined. This project aims to characterize the local metabolic framework generated by dysbiotic bacteria colonizing the intestinal adenomas through a multi-omic approach.
Requirements: Skills: ability to work with eukaryotic and prokaryotic cells. Preferred: background in cellular immunology and microbiology. Experience with human primary cells
Role of extracellular vesicles (EVs) in modulating inflammatory processes
Requirements: Knowledge of the main biochemistry and molecular biology techniques; ability in handling cultured cell line models.
Role of the (sphingo)lipid metabolism in the fibrotic process of patients affected by glaucoma
Requirements: Knowledge of the main biochemistry and molecular biology techniques; ability in handling cultured cell line models.
Increasing evidences point to iron as an important determinant of pancreatic islet inflammation and as a biomarker of diabetes risk and mortality. Iron metabolism in the β cell is complex: excess free iron is toxic but, at the same time, iron is required for β cell function and thereby glucose homeostasis. The aim of the research project is the understanding of the role exerted by iron transporters in islet physiology and pathophysiology by means of molecular, biochemical, pharmacological, and biophysical approaches in clonal β-cell lines and human islet.
Requirements: Expertise in cell biology and/or molecular biology. Interests and predisposition for fluorescence microscopy techniques and/or electrophysiology
Unravelling sensory-motor disfunctions caused by neurological disorders. In specific the project investigates functional limitations of gait and balance, and the value of advanced technological systems to improve or prevent functional loss.
Requirements: The candidate should be familiar with knowledge on anatomical and physiological mechanisms of the central nervous system. Furthermore, she/he should be familiar with pathology-induced effects of neurological disorders on the sensory-motor system.
New therapeutic approaches to neurodegenerative disease with particular interest in Parkinson’s Disease. In particular, using in vitro and in vivo experiments we are interested to understand the biochemical mechanism behind neurodegenerations: toxin protein accumulation (i.e. alpha-synuclein) mitochondrial disfunction and glia/microglia activation.
Requirements: Experience in biochemical, medical, biotechnological and pharmaceutical research
Role of inflammasome and phagocytosis in the pathogenesis of neurodegenerative diseases (Alzheimer Disease, Multiple Sclerosis, Parkinson Disease). Experiments ex vivo using leukocytes from patients to verify efficacy of neo-synthetic molecules able to down regulate NLRP3 inflammasome activation and to reduce pyroptosis and IL-1β and IL18 synthesis and to restore phagocytic function by TREM2 activation.
Requirements: Knowledge of cellular and molecular immunology with omics approach
In vivo human studies of exercise-stimulated metabolism to elicit anti-inflammatory and immunomodulatory responses in dysmetabolic conditions. In particular, it wil be covered: incremental exercise testing in normal weight, overweight/obese subjects, and athletes - measurements, clinical indications, and metabolic determinants related to energy metabolism.
Requirements: Good knowledge of the anatomical and physiological aspects of neuro-endocrine-muscular systems.
Etiopathogenetic study and translational medicine research applied to neuromuscular and neurodegenerative diseases.-- Neurodegenerative diseases represent a broad category of diseases with a high disability and mortality. Currently, novel therapeutic approaches are changing the natural history of some of these disorders. The project will focus on the development of new cell-mediated and/or molecular therapeutic approaches, both in in vitro and in vivo disease models.
Requirements: Experience in cell culture and molecular biology
The study will investigate the hypothesis that bone cells talk with parathyroid cells to modulate the PTH secretion and the availability of calcium for the bone matrix mineralization. The project aims to the study the crosstalk between bone and parathyroid tumor cells in parathyroid tumors and in patients with primary hyperparathyroidism, analyzing: 1) the role of carboxylated and uncarboxylated osteocalcin; 2) the role the bone-derived molecules of the WNT pathway; 3) the role of RANKL, 4) the role of circulating microRNAs.
Requirements: Experience of cell culture, molecular biology, transfection and gene silencing, western blot, immunofluorescence
Development of cellular and molecular therapeutic approaches for motor neuron diseases -- The current absence of effective therapeutic strategies for the treatment of highly disabling and often fatal motor neuron diseases requires a continuous research effort in this area. The project will be focused on the study of molecular pathogenetic mechanisms and/or the development of new gene, and molecular therapies through the use of patient-specific in vitro 2D (induced pluripotent stem cells- derived motor neurons) and 3D (central nervous system organoids) models.
Requirements: Experience in cellular and molecular biology
Vascular calcification (VC) is a major feature of the increased cardiovascular risk in end stage renal disease (ESRD) patients. The aim of this project is to study the effect of uremic toxins on vascular smooth muscle and endothelial cells and to setup a new in vitro model of co-colture, to better understand the pathogenesis of VC in uremia
Requirements: Cell Colture, Western-blot, Real time PCR
Uremic toxins middle molecules (MM) accumulate in Chronic Kidney Disease (CKD) patients. Several MM play a role in the pathogenesis of chronic inflammation and immunodeficiency.The aim of this project is to study the association of MM levels with clinical parameters and biological significance of SARS-Cov-2 infection in CKD patients.
Requirements: Cell Colture, Western-blot, Real time PCR
Detection of SARS-CoV-2 in different types of clinical specimens, assessment of the viral shedding, and of the transmission routes.
Requirements: Knowledge of basic techniques of cell biology (maintenance in culture of cell lines ) and molecular (nucelic acid isolation, PCR)
Morphological and molecular analysis of the epidermal barrier after different physical and chemical stimuli
Requirements: Good knowledge of cell and molecular biology
Morphofunctional analysis of the interactions between exogenous molecules and the intestinal barrier involved in the inflammatory cutaneous diseases
Requirements: Good knowledge of cell biology
Central organization of the postural control associated with voluntary movement, either in healthy subjects or in patients affected by movement disorders.
Requirements: Deep knowledge of motor and posture Physiology in Humans
Characterization of the immune mechanisms involved in the response against viral infections (HIV, HTLV-1, SARS-CoV-2) and identification of putative countermeasures. The project includes: 1. Characterization of immune regulation. 2. Characterization of factors involved in disease progression and viral replication. 3. Identification of putative interventions by pharmacological repositioning and novel strategies.
Requirements: Knowledge of cellular and molecular immunology
Identification and functional validation of new candidate genes in patients with rare endocrine diseases by combined NGS analyses (WES, targeted, WGS): in vitro and /or in vivo studies. Set up of spheroids cultures form normal and neoplastic tissues to test the efficacy of new therapeutic compounds.
Requirements: Knowledge in endocrinology, basic-level skills in next-generation sequencing techniques, cellular cultures and statistics applied to biomedical research.
Three-dimensional prostate model use and Augmented-reality during robotassisted radical prostatectomy. The preservation of erectile function and urinary continence is crucial to improved quality of life in prostate cancer survivors. In this research, we will assess the role of robot-assisted technologies to avoid any damage to the loco-regional neuro-vascular structures during prostatectomy.
Requirements: Solid theoretical-practical background in the field of oncologic prostate pathology and its surgical treatment using robot-assisted technologies.
Predictive and complementary biomarkers in HER2+ breast cancer. The project will combine histology, immunohistochemistry and next-generation sequencing techniques on tissue and liquid biopsy samples to identify clinically relevant subgroup of patients.
Requirements: Theoretical-practical knowledge of the main molecular pathology techniques, as well as mastery of the most common digital media including Windows, Office, image processing tools and social media.
Characterization of the effect extracellular matrix components, tumor microenvironment and 3D arrangement on carcinoma progression
Requirements: Knowledge of cell and molecular biology
Study of collagen turnover and expression of genes and proteins involved in extracellular matrix remodeling in connective tissue in physiological and pathological conditions, and after pharmacological treatment
Requirements: Knowledge of cell and molecular biology
Alterations of calcium homeostasis and role of the neuromuscular junction in the loss of muscle mass associated with prolonged microgravity and aging: the goal is to assess changes in the proteome, nitrosoproteome and lipids involved in the reduced efficiency of muscle contraction in muscle and serum of astronauts before and after 6 month of space flight and in active and immobilized elderly. The focus will be the calcium homeostasis dysregulation at the level of the neuromuscular junction.
Requirements: Availability to learn technologies aimed at proteo / lipidomic studies, the analysis of complex datasets using bioinformatics tools and team work.
Molecular studies of rare genetic diseases (chromatinopathies) to highlight the molecular basis of senescence. Project aims to identify the pathogenetic mechanisms observed in chromatinopathies and in senescence-diseases, paving the way to identify a therapeutic approach to change these disorders into curable diseases.
Requirements: Basic knowledge of molecular and cellular biology techniques
Genetics of mitochondrial diseases (MD). MD are a group of diseases with high clinical, biochemical and molecular heterogeneity, caused by mutations in mitochondrial DNA or nuclear DNA. New sequencing technologies have greatly improved mutational analysis for MD. This study aims to exploit new approaches (e.g. long reads NGS, whole RNA sequencing, single cell transcriptomics) to increase the diagnostic rate and accelerate novel disease gene discovery.
Requirements: Experience in NGS. Knowledge of molecular biology
Three-dimensional analysis of human craniofacial morphology in normal subjects and dysmorphic patients
Requirements: Basic information of the anatomy of the soft and hard tissues of the head
Morphological and metrical analysis of the skeleton: study of the biological variability in clinical, surgical and anthropological fields
Requirements: Basic information of osteology
Sphingolipid metabolism and signaling as a therapeutic target in tumor cells. The research project aims to study sphingolipid-mediated signal transduction mechanisms in physio-pathological processes with the aim of identifying targets for the development of innovative and effective therapies against tumors. In particular, the metabolism and the functional properties of specific sphingoid mediators will be investigated in the tumorigenicity of tumor and /or cancer stem cells.
Requirements: Basic knowledge of the experimental procedures used in a biochemical research laboratory
Integrated approach for the characterisation of bacterial virulence factors, host immunity and microbiota in infections caused by multi-resistant bacteria: identification of possible targets for intervention. The project includes the characterisation by sequencing of the bacterial genome with the identification of virulence factors, the study of innate immunity and the analysis of the microbiota (intestinal and pulmonary)
Requirements: Knowledge of the pathogenetic basis of infectious diseases, knowledge of omics approaches.
Translational research on biological material from covid-19 patients to understand the mechanisms of disease and identify therapeutic targets also to cope with future epidemics. Objective: to investigate the immunological, genetic and epigenetic characteristics of patients with acute SARS-CoV-2 infection and the molecular characteristics of the virus, to understand the disease mechanisms and host factors associated with the different degrees of severity of the clinical course. The ultimate goal of the project is to improve clinical practice in disease management and to identify possible therapeutic and vaccine prevention targets.
Requirements: Knowledge of the pathogenetic basis of infectious diseases, knowledge of immunology and omics approaches.
Pathophysiology and treatment of acute respiratory failure and personalization of ventilatory support in patients with and without coronavirus disease (COVID-19). Study of mechanical ventilation techniques and spontaneous breathing supports
Endothelial dysfunction, hemostasis and mechanism of organ damage in liver diseases. The endothelium is involved in the pathogenesis of acute and chronic liver damage. Von Willebrand factor (VWF) is a common marker of endothelial dysfunction and is an independent predictor of severe outcome in liver diseases. Objectives: 1) describing the pathogenic mechanisms regulating the hyperproduction of VWF, 2) defining the mechanism by which VWF is mediator of liver damage and potential target of therapy.
Requirements: The candidate must be highly interested in translational medicine. Clinical and/or scientific experience in the field of hepatology, in the use of animal models in research will be preferred skills.
Investigation of the molecular mechanisms underlying the cross-talk between cancer cells and their microenvironment. It will be evaluated how cells of the tumor microenvironment affect the growth and development towards the metastatic phenotype of cancer cells, focusing on the role of the tumor cell mithochondrial dynamics in this cross-talk. Aim of this project is the identification of molecular markers and possible targets for novel therapeutic strategies in terms of precision medicine.
Requirements: Basic knowledge of Cell Biology
Environmental and genetic factors strongly influence the pathogenesis and evolution of non-alcoholic hepatic steatosis (NAFLD). The project will evaluate the interaction between genetic variants, epigenetic modifications and nutritional intake in patients with histological diagnosis of NAFLD, in in vitro models genetically modified by CRISPR-Cas9 techniques and in mouse models of hepatic steatosis. The study will be implemented with omics techniques that will allow to define non-invasive markers for the identification of patients at risk of progressive disease.
Autonomic nervous system assessment to optimize training in elite athletes and to optimize exercise prescription for cardio‐metabolic and cancer treatment/prevention
Requirements: Knowledge at introductory level of exercise physiology, elements of physiology of autonomic nervous system and etiopathogenetic mechanisms of cardio‐metabolic diseases and cancer
The cytoskeleton protein filamin A (FLNA) plays a crucial role in endocrine tumors behaviour, regulating responsiveness to pharmacological therapy and invasiveness. The aim of the present project is to test the effects of a recently discovered FLNA inhibitor, PTI-125, on cell proliferation and on the expression/function of the receptors target of pharmacological therapy that are regulated by FLNA in different endocrine tumors (pituitary, adrenocortical and medullary thyroid tumors).
Requirements: Cell cultures; cell transfection and silencing; protein detection (western blot, co- /immunoprecipitation); cell imaging, cell proliferation, apoptosis, migration assays; nucleic acid extraction, PCR
Cohesins involvement in pediatric tumors. Project aims at dissecting the functional role of cohesins mutations in etiology of pediatric tumors for assessing new possible therapeutic strategies.
Requirements: Experience with transgenic models
The molecular basis of the protein aggregation dependent neurodegenerative diseases: structural and dynamic requirements for the protein-oligosaccharide interaction mediating protein aggregation and deposition.
Requirements: Previous laboratory experience with knowledge of the main biochemical techniques
Personalized treatment and stratification of breast cancer. Breast cancer is the most frequently diagnosed cancer in women, although its clinical outcome is strongly influenced by the molecular subtype. The project will focus on the development of patient-derived organoids and liquid biopsy approaches, based on the analysis of circulating tumor cells and extracellular vesicles, using advanced analytical methods in order to accurately recapitulate tumor heterogeneity, identify patients at risk and predict response to treatment, to allow for proper clinical management.
Requirements: Manipulation of patient-derived organoids and tumor cell lines. Handling of samples for histology, immunohistochemistry, flow cytometry and immunofluorescence. Use of chromogenic, fluorescence and/or bioluminescence assays. Knowledge of the main biochemical techniques functional to the characterization of serum biomarkers.
Nanomedicine plays a key role in the development of new diagnostic and therapeutic approaches for cancer. The goal of this project is the development of protein nanoparticles, which convey drugs or diagnostic tracers to the tumor, improving the therapeutic index and diagnostic accuracy. These nanoparticles will be characterized from a chemical and structural point of view and their interaction with biological systems will be studied in vivo and in vitro.
Requirements: Handling of rodents for biodistribution and activity/toxicity studies of nanoformulates in vivo. Manipulation of tumor cell lines and evaluation of interaction with nanoparticles by immunofluorescence, flow cytometry and fluorescence, luminescence and specific chromogenic assays. Knowledge of the main biochemical techniques functional to the bioengineering of protein nanoparticles for the development of drugs and fluorescent tracers.
Real-time analysis of body centre of mass displacement to detect individual locomotion features/anomalies
Requirements: Interest/knowledge in physiology and biomechanics of locomotion
Biomechanical adaptation and metabolic sustainability of human locomotion in hypo- and hyper-gravity conditions
Requirements: Interest/knowledge in exobiology, physiology and biomechanics of locomotion
Real-time analysis of body centre of mass displacement to detect individual locomotion features/anomalies
Requirements: Interest/knowledge in physiology and biomechanics of locomotion
Biological markers associated with Angelman syndrome (AS): AS is a severe neurodevelopmental genetic disease caused by imprinted UBE3A gene alterations. We have investigated neuropathology-related genes and proteins in hippocampus, pre-frontal cortex and blood samples of AS mice to pinpoint new markers associated with the condition and useful to monitor new drugs. The research is now aimed at evaluating these molecular markers in blood from AS patients collected at a dedicated biobank.
Requirements: Expertise in next generation sequencing (NGS) techniques: exomic squencing, RNASeq, and MethylSeq. Experience in the bioinformatic evaluation of gene variants, gene expression, and DNA methylation results.
One of the major problems associated with cancer therapy is the development of resistance to conventional care. It is therefore important to understand the mechanisms underlying chemoresistance in order to be able to design new anticancer agents. The proposed study aims to analyze the potential antitumor role and the associated mechanism of action of different natural compounds, in "in vitro" models of human tumors, in order to pave the way for new antitumor therapeutic strategies.
Requirements: Basic knowledge in cell cultures, molecular and cell biology techniques and fluorescence microscopy.
Elucidating the Mechanism of Reactive Oxygen Species Production in Thalassemia: A New Therapeutic Target. Oxidative damage by reactive oxygen species (ROS) contributes to cell and tissue injury in thalassemia. ROS generation in thalassemia occurs as a result of iron overload and anemia; however, the sources of ROS remain poorly understood. The project aims i) to identify and inhibit the sources of ROS in a mouse model of thalassemia; ii) to evaluate the oxidative damage and complications in a cohort of thalassemia patients to establish if data obtained in the mouse model can be relevant in humans.
The role of chaperone-mediated autophagy (CMA) in Temozolomide resistance in glioblastoma (GBM) will be evaluated in cell lines and patient-derived samples. Gene expression profiles, miRNA levels and the activity of specific metabolic pathways will be evaluated to understand the role of CMA differential regulation and its role in the resistance to treatment. CMA modulators will be assessed both in vitro and in orthotopic animal models of glioblastoma by non-invasive optical imaging techniques.
Requirements: Interest in neuro-oncology, curiosity and ability to work in a team
3D-modeling of glioma. Glioblastoma (GBM) exploits different ionic pumps and bioenergetics molecule to sustain glioma stem cells and to thrive in the brain microenvironment. Ionic pumps signature correlates with deregulation of epigenetic enzymes. The aim of the study is to understand, using primary 3D-GBM cultures, animal models and OMICS techniques, how these ionic pumps may integrate bioenergetics and epigenetic signaling, altering the microenvironment and favoring tumor progression.
Requirements: Highly motivated in partecipating in a translational research project in a multidisciplinary environment.
Development of biomarkers for the evaluation of red blood cell turnover. In patients with chronic hemolytic anemia, in particular in hemodialysed patients in treatment with erythropoietin, red blood cell population is younger respect to healthy controls. The project is aimed to the development of biomarkers of red blood cell age, by studying proteins, circulating miRNA and metabolites related to red cell turnover.
Requirements: Competences in the measurement of cellular metabolites and enzymes. Basic knowledge of clinical molecular biology techniques.
Study of the activity of HSP90 inhibitors as new leishmanicidal and antimalarial agents. Evaluation of the effect of HSP90 modulation in different stages of development of the two parasites.
Requirements: Knowledge of basic elements of cellular biology
The human body can be more understood if considered as a whole. This research line will exploit the holistic approach based on high throughput "-omics" technologies for deciphering the intricate, and common processes that underlay the genesis of gastro-hepatic disease, obesity, insulin intolerance, metabolic syndrome, diabetes, and ultimately, cardiovascular diseases in humans. This will hopefully lead to the discovery of new molecules acting as common biomarkers in the Precision Medicine era.
Requirements: Experience in Separative Techniques and Mass Spectrometry. Manipulation, purification and extraction of bioactive substances from biological matrices. Quantitative and statistical procedures.
Hypoxia, represents a common adverse feature in diseases as respiratory distress syndrome (ARSD) and chronic obstructive pulmonary disease (COPD). By contrast, at altitude, the human body orchestrates a defense against hypoxia by activating adaptive responses. This research is aimed to investigate the determinants of the double face of hypoxia by studying the systemic response of the body in terms of "–omics" profiles in serum of healthy, healthy hypoxic and diseased hypoxic patients.
Requirements: Experience in Separative Techniques and Mass Spectrometry. Manipulation, purification and extraction of bioactive substances from biological matrices. Quantitative and statistical procedures.
COVID-19 is responsible for a systemic disease that eventually involves several pathways linked to both metabolome and lipidome, and targets multiple organs (lungs, liver, kidney) impairing their function and leading to multi-organ injury. The main goal of this study is to fill the knowledge gap regarding the composition of the lipids and metabolites signature alterations in COVID-19 pneumonia patients, in particular by studying the changes occurring with the increasing severity of the disease
Requirements: Experience in Separative Techniques and Mass Spectrometry. Manipulation, purification and extraction of bioactive substances from biological matrices. Quantitative and statistical procedures.
Identification of therapeutic targets in anorexia nervosa (AN). We will study >70 AN patients (BMI<16, at least one affected family member) and >100 patients with sporadic AN by NGS analysis to identify variants associated to this disease. Natural molecules and/or FDA approved drugs will be tested in cell lines, and their mechanisms of action will be explored to restore altered gene function through RNA and molecular targets analysis, shedding light on the pathophysiology of AN.
Requirements: Knowledge of the principal diagnostic techniques for high-throughput genetic research
Biomechanics and bioenergetics of human locomotion in simulated hypogravity. The analysis of metabolic cost and mechanical work of human gaits in simulated hypogravity will define and optimize the gait choices during different tasks on celestial bodies with lower gravity than on Earth.
Requirements: knowledge of muscle and locomotion physiology and biomechanics; skills in data analysis also with purposely written software.
The role of enhanced von Willebrand factor (VWF) clearance in the pathogenesis of partial VWF deficiency using advanced biochemical and genetic approaches. While enhanced clearance of von Willebrand factor (VWF) is associated with the etiology of von Willebrand disease (VWD), the cellular and genetic background of this issue is not well defined. To address this, the genetic defects in the VWF gene that associated with a shorter half-life of VWF will be investigated. Furthermore, the role of the oligosaccharide chain composition of VWF in the pathogenesis of VWD as well as VWF half-life will be evaluated using specified glycosylation assay.
Requirements: The candidate must have experiences in Biochemistry and Molecular and Cellular Biology
Despite recent advances in diagnostic method and treatment, coronary artery disease (CAD) remains the primary cause of morbidity and mortality. It is widely accepted that genetic factors play an essential role in its development. The aim of this project is to investigate the genotypic and phenotypic risk factors associated with prognosis for coronary artery disease in the young (Iranians) with the purpose to identify predictive biomarkers and new molecular targets.
Requirements: The candidate must have significant experience in Molecular Biology and bioinformatics skills in genomic data analysis
Role of the small airways in the physiopathology of pulmonary diseases, with particular reference to the effects of small airways cyclic opening and closing in patients with chronic obstructive pulmonary disease (COPD) and in animal models.
Requirements: Knowledge of respiratory physiology, biophysics and/or biomechanics.
In vitro and in vivo study of disturbances of the acid-base balance in critically ill patients and comparison with data collected from non-critical and healthy volunteer patients. Role of hydro-electrolytic alterations, plasma proteins and hemoglobin on the acid-base balance
Extracorporeal techniques for organ support in respiratory and renal failure. Development and evaluation of new extracorporeal carbon dioxide removal and dialysis techniques. Optimization of efficiency and biocompatibility
Platelet activation in patients with immune thrombocytopenia. The project plans to study platelet activation in patients with immune thrombocytopenia with a different clinical phenotype, i.e. hemorrhagic or thrombotic, evaluating the modulation of therapies. Platelet activation will be evaluated ex vivo through flowcytometry and using a microfluidic platform. This system simulates the conditions of the blood flow and allows to evaluate platelet thromboformation by varying analytical conditions.
Requirements: Previous laboratory experience with knowledge of the main biochemistry
Physiological regulatory mechanisms and development of postsurgical adverse events - Network Physiology (NP) is an emerging field of computational physiology that allows to study the cardiovascular and cerebrovascular regulatory systems and their dynamical interactions. The project will evaluate associations between the functioning of physiological control mechanisms, as assessed via typical NP methods before major cardiac surgery, and the development of postoperative cardiovascular and cerebrovascular adverse events.
Requirements: Expertise in biomedical signal processing and statistics.
Evaluation of the role of the autonomic nervous system on cerebrovascular autoregulation in physiological conditions and in critical situations - Cerebrovascular autoregulation is a fundamental mechanism for maintaining adequate cerebral perfusion in the presence of blood pressure changes. The autonomic nervous system plays an important role in the regulation of vascular resistances. The project will use advanced signal processing techniques to characterize the interaction between the autonomic nervous system and cerebrovascular autoregulation in physiological conditions and in critical situations.
Requirements: Expertise in biomedical signal processing and statistics.
Physiological mechanisms of cardiac neural control during physical exercise and recovery - An impairment of the cardiac neural control during physical exercise and recovery phase can expose the subject to the risk of arrhythmic events. The project will use advanced time series analysis techniques for the indirect assessment of the cardiac neural control during maximal physical exercise and the return to baseline situation.
Requirements: Expertise in biomedical signal processing and statistics.
Role of sphingolipids in the mechanism of repair of damaged myelin, with focus on multiple sclerosis.
Requirements: Knowledge of the basics of sphingolipid biochemistry. Knowledge of the techniques of cell culture.
Combining whole exome and RNA sequencing to identify genetic defects and molecular pathways in muscular dystrophies (MD). The candidate will apply NGS-based sequencing techniques to a cohort of undiagnosed MD patients. Molecular, histological and biochemical studies in patients’ muscle and cellular models will be used to investigate disease pathogenesis and to develop therapeutic approaches.
Requirements: Basic knowledge in cell culture and in molecular biology, curiosity, motivation.
The project aims to evaluate the effect of a structured Incremental and Aerobic Exercise intervention on quantity and quality of nocturnal sleep and on potential metabolic modulators of BRCA penetrance in breast cancer women with BRCA mutations.
Requirements: Skills in adapted physical activity. Use of the actigraphy for sleep analysis and activity levels. Experience in the administration of exercise programs.
Artificial intelligence for cardiovascular imaging biomarkers
Requirements: Basic knowledge of medical imaging techniques and of radiomics and machine/deep learning
Optimization of contrast media utilization in medical imaging
Requirements: Basic knowledge of medical imaging techniques and contrast agents
Artificial intelligence applied to radiological images to improve diagnosis and prognosis of high-impact disease in the female population
Requirements: Basic knowledge of medical imaging techniques and of radiomics and machine/deep learning
Three-dimensional analysis of human movement in health, disease and sports
Requirements: Basic information of the anatomy of the human locomotor system and biomechanics
Two research lines: 1. Study of the molecular mechanisms that alter the synthesis, transport and consume of lipids in Cystic Fibrosis. Clinical study of metabolic alteration associated with lung transplant rejection in Cystic Fibrosis patients. 2. Study of the molecular mechanism induced by the therapeutic application of Transcranial direct current stimulation (tDCS) in Parkinson’s disease models; clinical study of lipid metabolism alteration in patients.
Requirements: Personal interest in clinical research. Basic knowledge in Biochemistry and Molecular Biology.
Study of the effects of extracellular vesicles (EVs) secreted by lung tumor cells on macrophage polarization. It will be evaluated how the phenotype acquired by macrophages upon interaction with EVs can affect the outcome of different types of immunotherapeutic regimens utilized for the treatment of lung cancer. Moreover, a deep analysis of EVs molecular content, able to influence macrophage polarization, will be performed.
Requirements: Experience in cellular and molecular biology
Study of the immune response to SARS-CoV-2 in HIV-infected convalescent and vaccinated subjects
Requirements: Knowledge of biology and/or medicine with possible experience in molecular and cellular biology techniques
Study of the gastrointestinal tract as a pathogenic site of HIV infection
Requirements: Knowledge of biology and/or medicine with possible experience in molecular and cellular biology techniques
Role of immune system in muscle homeostasis. This project will determine the role of the immune system in muscular dystrophies. First, we will used a combination of loss-of-function methods that specifically targeted regulatory T cells (Tregs) to examine if Tregs regulate the pathogenesis and progression of muscular dystrophy. Then, we will induce experimental immune tolerance by thymus transplantation and evaluate the effect of genetic or pharmacological interference with dendritic cells (DCs) cascade on disease severity. The final aim of this project is to provide an in-depth analysis of the role of central and peripheral immunity on muscular dystrophy that should be beneficial to the development of future therapeutic strategies.
Requirements: Knowledge of in vitro and in vivo cellular and molecular biology and experience in muscular dystrophy models.
Identification of new vaccine strategies for the generation of effective and lasting humoral and cell-mediated responses. 1. Evaluation of the immune correlates of protection against infections (SARS-CoV-2, HBV, HIV, Meningococcus); 2. Pre-clinical analysis of humoral and cell-mediated immune responses to new vaccines; 3. Clinical validation of the response to new vaccines; 4) Analysis of the response to vaccines in fragile subjects (eg HIV-infected patients).
Requirements: Knowledge of cellular and molecular immunology with omics approach
The role of the lung microenvironment in graft rejection after lung transplantation: extracellular vesicles as molecular cargoes of inflammatory signaling. The immune and molecular mechanisms underlying rejection after lung transplantation are not fully known. The aim of the study is to understand the molecular messages carried by the microvesicles in patients undergoing lung transplantation in order to elucidate the pathological mechanisms underlying acute and chronic rejection.
Requirements: Highly motivated in partecipating in a translational research project in a multidisciplinary environment.
The goal of the lab research will be to identify and characterize genetic variants predisposing to liver disease and COVID-19 exploiting NGS analyses in large cohorts. Functional studies will be conducted both in vitro, exploiting genome-editing strategies, and in vivo to understand the biological mechanisms underlying the genetic association. Results will improve patients risk stratification and pinpoint novel therapeutic targets in a precision medicine perspective.
Requirements: Competence in molecular biology and/or bioinformatics
To assess whether the magnitude and aetiology of neuromuscular fatigue are similar between upper- and lower-limb muscles of the same subjects during different types of exercises. This by studying the changes both in the corticospinal and in the muscle excitability and with a translational approach.
Requirements: Basic knowledge of: (i) exercise physiology, (ii) neuromuscular physiology, (iii) physiological adaptations to physical exercise.
Innovative and alternative therapeutical approaches for drug-resistant epilepsy
The involvement of microbiota-gut brain axis in neurovelopmental disorders
Extracorporeal supports for ex-vivo and in-situ organ perfusion. Optimization and development of extracorporeal supports for the evaluation and reconditioning of solid organs before transplantation

Courses list

November 2021
Courses or activities Professor(s) ECTS Total hours Language
Optional
Cardiovascular interactions 3 16 English
February 2022
Courses or activities Professor(s) ECTS Total hours Language
Optional
Biomarkers in precision medicine: bridge the gap between translational research and clinical practice 2 14 English
Evaluation of physical exercise - 2021 update 2 14 English
How to communicate your research 2 10 English
Laboratory diagnostics and clinical research 2 10 English
Proteomics and Lipidomics for disease related biomarkers discovery: technical aspects and applications 2 10 English
The double face of the moon. Scientific papers: from authoring to reviewing 3 15 English
March 2022
Courses or activities Professor(s) ECTS Total hours Language
Optional
2D, 3D and 4D iPSC-derived cellular models to study neuromuscular diseases 2 12 English
Genetic and molecular diagnosis in endocrine diseases 2 10 English
Osteocalcin: one molecule, multiple functions in aging and frailty 2 10 English
April 2022
Courses or activities Professor(s) ECTS Total hours Language
Optional
Hemostasis and inflammation: from molecular aspects to organ damage 2 10 English
Single Cell Analysis for biomolecular and matobolomic pathways discovery 2 12 English
May 2022
Courses or activities Professor(s) ECTS Total hours Language
Optional
Autonomic nervous system regulation in elite sport and exercise 2 10 English
Exercise Medicine 2 10 English
Spectroscopy and imaging of biosystems on the nano-, meso- and macro-scale. 3 18 English
June 2022
Courses or activities Professor(s) ECTS Total hours Language
Optional
Cancer network biology: experimental approaches towards precision medicine 4 40 English
Psychiatric Neurosciences 2 10 English

Enrollment

Places available: 23

Call for applications

Please refer to the call for admission test dates and contents, and how to register.

Session: 1

Application for admission: from 28/05/2021 to 28/06/2021

Application for matriculation: from 26/07/2021 to 16/08/2021

Read the Call


Attachments and documents

Attachments to the call

Qualifications Assessment

Evaluation Results

Session: 2

Application for admission: from 15/10/2021 to 08/11/2021

Application for matriculation: from 18/11/2021 to 22/11/2021

Read the Call


Attachments and documents

Attachments to the call

Extension

Attachment 1

Qualifications assessment

Evaluation Results

Research lines assigned