Translational Medicine

Dottorati
Doctoral programme (PhD)
A.Y. 2019/2020
Study area
Medicine and Healthcare
Doctoral programme (PhD)
3
Years
Dipartimento di Scienze biomediche per la salute - Via Mangiagalli, 31 - 20133 Milano
English
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.
Dipartimento di Scienze biomediche per la salute - Via Mangiagalli, 31 - 20133 Milano
Title Professor(s)
History and geography of tumor infiltrating lymphocytes. Lymphocytes heterogeneity in the tumor microenvironment (TME) is a major challenge for the elucidation of the immune responses that block or promote tumor growth. The study will try to identify cellular identity and spatial location of lymphocytes at tumor sites, thus will helping in designing new immunotherapeutic strategies.
Requisiti: For students who have done an experimental graduation thesis using cell biology and/or molecular biology.
Effects of stress hyperglycemia according to diabetic status in patients with ST-elevation myocardial infarction and its relationship with cardiac cell injury and mitochondrial damage: a translational approach.
Multidisciplinary approach to monitoring and tracking player health, performance and fatigue-recovery continuum in young soccer players. 1.assessment of body composition, field-based performance tests 2.integrated framework of health and performance monitoring by a combination of applications and non-invasive methods 3.translating evidence into practice in the field of modern football
Requisiti: Knowledge of applied research principles, ability to translate research results into practical advices, knowledge and experience in the use of non-invasive monitoring methods
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.
Requisiti: Cell culture, lipid analysis, enzymatic assays
Studying the effect of the over-expression and silencing of specific miRNA, altered during training and aging, on the electrophysiological properties of the sinus node, using sinoatrial-like cardiomyocytes derived from engineered mouse embryonic stem cells (mESC) and induced pluripotent stem cells (iPSC).
Requisiti: Competences in cellular electrophysiology (patch clamp), stem cell biology and molecular biology.
Study of the molecular mechanisms associated with the sinus node syndrome and related arrhythmias
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.
Requisiti: Basic knowledge in cell culture and in molecular biology
High cognitive functions and functional organization of motor cognition in humans
Characterization of new factors involved in antigen presentation mechanism responsible for cellular-mediated immune response. Effects on anti-tumural and anti-viral immune responses. The project will be divided into 3 steps: Identification and functional characterization of ERAP2 gene polymorphisms Evaluation of the cytotoxic immune response in the presence of the different ERAP2 gene variants Functional characterization of ERAP2 gene variants in susceptibility to viral infections and colon cancer
Requisiti: Knowledge of cellular and molecular immunology with omics approach
My area of study is that of asymptomatic and symptomatic stages of multiple myeloma (MM). The overall aim of the project is to identify initiating lesions in MM and differentiate them from lesions relevant for progression. This could lead to novel diagnostic tests with predictive value for patients, and provide novel targets for rationale treatment.
Requisiti: Experience in handling patient samples, cell purification, and nucleic acid extraction. Knowledge of molecular biology techniques
Understanding Candida auris pathogenesis to overcome the emerging fungal challenge. Candida auris an emerging multidrug-resistant pathogen has been reported in several countries being implicated in nosocomial outbreaks. Commonly,C. auris is resistant to the first-line antifungal drug fluconazole and can rapidly evolve to develop resistance to other antifungal drugs. As a result, C. auris has attracted attention worldwide despite the limited pathogenesis knowledge base.
In this project, Machine Learning approaches (computational strategies that automatically determine (i.e., learns) methods and parameters to reach an optimal solution to a problem) will be used to assess the prognostic trajectories of psychiatric subjects. Specifically, a multimodal longitudinal approach, combining structural and functional imaging data with clinical and cognitive performances, will be applied in order to look for brain patterns and biomarkers in a psychiatric population.
Requisiti: Basic knowledge of Machine Learning techniques and of coding languages (Matlab or R); knowledge of brain imaging
Analysis of the effects of vitamin D on the electrical activity of the cardiac sinoatrial node
Biomarkers associated with the diagnosis of Mood Disorders: epigenetic, inflammatory and hormonal factors involved in the etiology and outcome of Mood Disorders
Requisiti: Competence in the field of translational research and/ or molecular biology
The project will address genetic, molecular and cellular aspects linked to the pathogenesis of serpinopathies, a class of conformational diseases each caused by mutations in a specific serpin. These proteins are particularly vulnerable to point mutations. These mutations often lead to the polymerization of serpins within the cells of synthesis, with consequent local damage associated with the accumulation of polymers and defect of secretion with loss of the inhibitory function. The proposal will focus on the deficiency of the serpin C1-inhibitor, which causes hereditary angioedema.
Requisiti: Basic knowledge of cellular and molecular biology.
Alzheimer’s disease: linking protecting/promoting clinical evidence and structural features. The central feature in AD pathogenesis is the accumulation of neurotoxic forms of Aβ-peptide which aggregate from small soluble oligomers to extended fibers. It has been clinically observed that some naturally-occurring variants of Aβ do protect from this disease. We propose to study the molecular machinery underlying the actual protective/promoting effects of different genetic variants of Aβ. 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 and the Besta Institute
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.
The intestinal compartment is composed by immune cells, epithelial cells and gut microflora involved in functional crosstalks aimed at maintaining a balance between tolerance and immunity. In vitro systems, murine models of intestinal inflammation, and patients’-derived surgical specimens, will be used to investigate how the intestinal microenvironment, including the gut microbiota, affects mucosal T cells activation during IBD (Inflammatory Bowel Disease) progression.
Requisiti: Previous experiences in Biology or Biotechnology fields; knowledge of molecular and cellular biology techniques, cytofluorimetry and in vivo mouse models of intestinal inflammation.
Platelets from Cystic Fibrosis (CF) patients exhibit a mutated CFTR channel and are hyper-activated and pro-inflammatory. This proposal aims at: 1. characterizing the functional role of the CFTR channel in healthy platelets and in an in vitro model of CF - platelets; 2. evaluating the therapeutic efficacy of extracellular vesicles released by human mesenchymal stem cells in controlling the hyper-responsive platelets from patients affected by Cystic Fibrosis.
Requisiti: Knowledge of the main biochemistry and molecular biology techniques; ability in handling in vitro model of cultured cell line
Iron may be an important determinant of pancreatic islet inflammation and 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 project aims to understand 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.
Requisiti: Expertise in cell biology and/or molecular biology. Interests and predisposition for fluorescence microscopy techniques and/or electrophysiology.
Study of platelet hyper-reactivity: its association with the risk of atherothrombotic coronary artery disease, identification of its molecular bases and functional characterization.
Requisiti: Knowledge of basic elements of cellular biology
New therapeutic approaches to the sporadic Parkinson’s Disease. The proposal seeks to explore the molecular role played by the oligosaccharide II3Neu5Ac-Gg4 in resolving the physiopathology of PD. In particular, using in vitro and in vivo experiments we are interested to understand the biochemical mechanism behind the PD neurodegenerations: alpha-synuclein accumulation, mitochondrial disfunction and glia/microglia activation.
Requisiti: 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.
Requisiti: Knowledge of cellular and molecular immunology with omics approach
Cryotherapy has been shown to reduce pro-inflammatory response, relieve pain and enhance muscles’ post-exercise recovery. In this project, several types of cryostimulation will proposed to investigate independent effects of cooling, under a variety of conditions, therefore gaining a possible neuro/muscular recovery after exercise or triggering cold-induced thermogenesis for combating overweight and obesity.
Requisiti: 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, there are no effective therapeutic strategies for these diseases. The project will focus on the development of new cell-mediated therapeutic approaches, based on the use of stem cells, and/or genetic and molecular therapeutic approaches, both in in vitro and in vivo disease models
Requisiti: Experience in cell culture and molecular biology
The present proposal will investigate the role of the hormone osteocalcin released by osteoblasts during bone remodeling in the modulation of the PTH synthesis and secretion from parathyroid cells and on the parathyroid cell proliferation. Osteocalcin has been recognized as a hormone involved in glucose metabolism and male gonadic function regulation. The project will use primary cultures of human parathyroid cells derived from benign parathyroid tumors, and the established cellular model of the HEK293 cells transiently transfected with the calcium-sensing receptor CASR. The experimental proposal is part of the project founded by Bando Cariplo 2018 for Research Aging.
Development of cellular and molecular therapeutic approaches for neurodegenerative and motor neuron diseases -- The current absence of effective therapeutic strategies for the treatment of highly disabling and often fatal neurodegenerative and motor neuron diseases requires a continuous research effort in this area. The project will be focused on the study of molecular pathogenetic mechanisms through the use of patient-specific in vitro models (induced pluripotent stem cells) and / or the development of new gene, molecular or cell-mediated therapy approaches in pre-clinical in vivo models of these diseases.
Requisiti: Experience in cellular and molecular biology
One of the main features of the increased cardiovascular (CV) risk in end stage renal disease (ESRD) patients is vascular calcification (VC). One of the VC inducer is haemodialysis (HD) per se. Since the choice of dialyzer may play a role on prevalence of CV in ESRD, the aim of this project is to study the effects of new treatment with Expanded HD (Theranova dialyzer) on delay VC progression, using sera of ESRD patients in an in vitro model of rat VSMCs.
Requisiti: Cell culture, Western blot, Real-time PCR
Human Endogenous Retroviruses as biomarkers and target of therapy for the colon cancer. The project will be conducted analyzing the expression of the HERVs in tissues and exosomes from colorectal cancer patients, the methylation status of the HERV Long Terminal Repeat (LTR) sequences, and identifying HERVs proteins as target for immunotherapy. Cellular in vitro models and an in vivo model based on Zebrafish will be also set in order to confirm the data obtained ex vivo.
Evaluation of mechanisms of injury induce by UV-rays exposure and protective effects of polyphenolic compounds in 2D and 3D experimental human models.
Effects of pro-inflammatory cytokines involved in atopic dermatitis pathogenesis in a three-dimensional model of human normal skin: morphological and molecular analysis.
Study of energetic requirements of physical activity and sport-induced modifications related to energy metabolism, sports performance, morpho-functional modifications and hormonal regulation in sports and doping. Particular attention will be devoted to the study of changes induced by physical activity in populations with special needs and elderly, giving emphasis to the translationality of physical exercise and its use as a preventive and therapeutic tool.
Requisiti: The candidate should have good knowledge of the anatomical and physiological aspects of cardio-pulmonary, vascular and neuro-muscular systems. Furthermore, she/he should have a good knowledge of the physiological effects induced by aging.
Study of aspects related to neuromuscular activation and skeletal muscle contraction. Particular attention will be devoted to the study of changes induced by physical activity in populations with special needs and in the elderly, giving emphasis to the translationality of physical exercise and its use as a preventive and therapeutic tool.
Requisiti: The candidate should have good knowledge of the anatomical and physiological field of the neuro-muscular system. Furthermore, she/he should have a good knowledge of the physiological effects induced by aging and other neuromuscular pathologies.
Central organization of posture in Humans, either healthy or affected by movement disorders.
Requisiti: Deep knowledge of motor and posture Physiology in Humans
Characterization of immune responses involved in organ transplant maintenance/rejection: identification of countermeasures. The project includes three intervention strategies: 1. extracorporeal organ reperfusion for organ maintenance. 2. extracorporeal photopheresis for prevention of rejection. 3. identification of new early markers of rejection or infection.
Requisiti: Knowledge of cellular and molecular immunology with omics approach.
Monitoring for classic and newly discovered human Polyomaviruses infection after renal transplantation in order to perform early diagnosis of viral opportunistic infections in immunosuppressed patients. Set up of innovative neutralization assay for the discover of antibodies-based treatment of Polyomavirus-associated nephropathy.
Immunopathology of solid tumors. - In solid tumors the immunological milieu and alterations involving the DNA repair system affect the tumorigenesis and may modify the choice of personalized therapeutic protocols. Through an integrated approach (morphology, immunohistochemistry, next generation sequencing, bioinformatics tools), this project will study new tumor-specific biomarkers to identify alterations in such systems. The project will be done at the Division of Pathology of the Policlinico of Milan.
Requisiti: Knowledge of basic immunohistochemistry and molecular biology techniques as well as a strong motivation towards the study of immuno-pathology and immuno-oncology.
Identification and functional validation of new candidate genes in patients with rare endocrine diseases by combined NGS analyses (WES, targeted, WGS) and in vitro molecular approaches
Requisiti: Knowledge of endocrinology and metabolism, basic-level skills in next-generation sequencing techniques and statistics applied to biomedical research.
Characterization of the effect extracellular matrix components, tumor microenvironment and 3D arrangement on pancreatic ductal adenocarcinoma progression
Requisiti: Knowledge of cell and molecular biology
Identification of metabolic changes associated with osteoarthritis and obesity. Osteoarthritis causes the progressive loss of articular cartilage. The risk of developing osteoarthritis increases in overweight and obese. The aim of the project is to dissect signaling pathways from proteins and lipids in obese subjects with and without signs of osteoarthritis to identify early markers and new therapeutic targets.
Requisiti: Training in biochemical laboratory, interest in “omics” technologies and statistical analyses of complex data and bioinformatics.
Molecular study of epigenetic machinery disorders (chromatinopathies). Project aims to identify the molecular pathogenetic mechanisms and strategies able to rescue chromatin opening/closing defects observed in chromatinopathies, in particular in Rubinstein-Taybi patients, paving the way to identify a therapeutic approach to change these disorders into curable diseases.
Requisiti: Basic knowledge of molecular and cellular biology techniques
THE ROLE OF CERAMIDES AS BIOMOLECULAR MARKERS IN MOYAMOYA angiopathy (MA) PATHOGENESIS. MA is a rare, chronic and disabling cerebrovascular disease. The project will investigate the potential role of ceramides as blood biomarkers for MA patients with the long term objective to identify factors involved in a de - regulated hypoxia endothelial cellular response and in the caveolin - 1 /nitric oxide mediated signaling pathway. Moreover, the project will test the potential efficacy of ceramide de novo synthesis - inhibition as a strategy in cellular experimental models involving MA patient derived - c EPCs
Three-dimensional analysis of human craniofacial morphology in normal subjects and dysmorphic patients
Requisiti: Basic information of the anatomy of the soft and hard tissues of the head
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: a) invasiveness, chemoresistance, angiogenesis and the characteristics of staminality of tumor and /or cancer stem cells.
Requisiti: Basic knowledge of the experimental procedures used in a biochemical research laboratory
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: a) invasiveness, chemoresistance, angiogenesis and the characteristics of staminality of tumor and /or cancer stem cells.
Requisiti: Basic knowledge of the experimental procedures used in a biochemical research laboratory
Integrated approach for the characterization of bacterial virulence factors, host immunity and microbiota in infections sustained by multiresistant bacteria: identification of possible targets for intervention. The project involves the characterization through sequencing of the bacterial genome with identification of virulence factors, the study of innate immunity and the analysis of the microbiota (intestinal and pulmonary).
Requisiti: Knowledge of the pathogenetic basis of infectious diseases, knowledge of omics approaches.
Endothelial dysfunction and activation of hemostasis as mechanism of organ damage and target of therapy in liver diseases - Objectives: 1) describing the pathogenic mechanisms regulating the hyperproduction of Von Willebrand factor (VWF), a common marker of endothelial dysfunction and an independent predictor of severe outcome in acute and chronic liver diseases, 2) defining the mechanism by which VWF is mediator of liver damage and potential target of therapy.
Requisiti: The candidate must be highly interested in traslational medicine. Scientific experience in the field of hepatology, license for the use of animal models in research will be preferred titles.
Physical activity protocol to counteract the effects of sarcopenia in older people. Sarcopenia is characterized by generalized and progressive loss of muscle mass, reduction in muscle strength and resultant functional impairment. It has been demonstrated that increased physical activity is positively associated with muscle mass. For this reason we will evaluate the benefits of a physical activity protocol to counteract the effects of sarcopenia in older people
In-vitro study of the acid-base characteristics of patients with sepsis and septic shock. The aim of the project is to study in-vitro the acid-base equilibrium of septic patients and compare the obtained results with data gathered from critically ill non-septic patients and from healthy volunteers. The hypothesis is that the inflammatory state and the alter redox state, characteristic of septic patients, might induce structural changes of albumin and hemoglobin, the most important proteins of blood, which might result in an altered buffering function. As a result, septic patients would have a lower buffer power and would therefore be more exposed to acute acid-base derangements.
Requisiti: Good knowledge of the physiology of acid-base and of the following experimental techniques: in-vitro tonometry performed both on plasma and on whole blood, blood gas analysis. Interest for chromatographic and spectrophotometric techniques for study of protein structure.
Aim of this project is the investigation of the molecular mechanisms underlying the cross-talk between cancer cells and their microenvironment. Specifically, it will be evaluated the role of tumor cell-derived exosomes and their 'cargo' (miRNAs, proteins) on adipocytes and immune cells (neutrophils) functions. This project aims to pave the way for the identification of tumor-derived exosomes as diagnostic, prognostic and drug resistance-predictive markers in oncological patients (i.e., melanoma and advanced prostate cancer patients) in terms of precision medicine.
Requisiti: High motivation for basic research. Basic preparation in the field of the biology of tumor cells. Knowledge of cell and molecular biology techniques
Autonomic nervous system assessment to optimize training in elite athletes and to optimize exercise prescription for cardio‐metabolic and cancer treatment/prevention
Requisiti: Knowledge at introductory level of exercise physiology, elements of physiology of autonomic nervous system and etiopathogenetic mechanisms of cardio‐metabolic diseases and cancer
The mammalian reproductive functions are under the control of Gonadotropin-Releasing Hormone (GnRH), produced by hypothalamic neurons. Developmental alteration of such neurons, as well as of GnRH secretion, may lead to hypogonadotropic hypogonadism (HH) and, in particular to Kallmann's Syndrome (KS). A number of HH causative genes have been so far identified, but they only cover the 40% of diagnosed HH cases. New factors and mechanisms involved in the GnRH neuron development,  differentiation and migration are studied by using in vitro models. The effects of such factors on GnRH secretion and their role in the etiopathogenesis of HH are also investigated.
Requisiti: General expertise on cell biology/physiology lab's techniques; the student will acquire new technical skills on cell culture and transfection, gene and protein expression analysis, cell survival, proliferation, differentiation and in vitro migration assays and cell imaging.
Cytoskeleton actin-binding proteins as determinants and new biomarkers of pituitary tumor invasiveness and drug response. This project will test the role of actin-bindigng protein Cofilin as a biomarker for non-secreting pituitary tumor invasion and recurrence, as well as the role of citoskeleton protein Filamin A in modulating pharmacological sensitivity/resistance to somatostatin analogs in GH-secreting pituitary tumors.
Requisiti: Cell culture; cell transfection and silencing; protein detection (western blot, co-/immunoprecipitation); cell imaging (fluorescence microscopy), biochemical assays (cell proliferation, apoptosis)
"Autoinflammatory profile, activation of coagulation and thrombotic risk in cutaneous small vessel vasculitis: role of cytokines, neutrophil extracellular traps (NETs) and tissue factor"
Requisiti: Knowledge on the clinical manifestations and physiopathological aspects of vasculitides
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.
Ganglioside derivatives in neurodegenerative diseases and sphingolipidosis. Synthesis of ganglioside derivatives aimed at identifying proteins involved in the mechanisms of neurodegenerative diseases and sphingolipidosis. Synthesis of molecules for the diagnosis and / or treatment of neurodegenerative diseases and sphingolipidosis. The research will be carried out through the synthesis of organic molecules, purification by chromatographic techniques, analysis by HPLC-MS, NMR. Use of cell cultures.
The damping within joints and nearby tissues: its role in human healthy and prothesic locomotion. Effects on mechanical external and internal work, and on the metabolic cost of walking, running, skipping and cycling. Partitioning, within dissipative internal mechanical work, of prosthesis and connective tissue components, by means of passive limb oscillation and pendulum mechanical models.
Requisiti: Knowledge of Physiology and Biomechanics of muscle and of locomotion, software programming with Labview (National Instruments).
Development of novel biomarkers of maternal/placental origin for risk stratification in various pathologies of pregnancy, mostly related to overweight and obesity. miRNome analysis in blood and placenta.
Requisiti: Basic competences in cell biology and clinical molecular biology.
Evaluation of liver metabolism alteration in acute intermittent porphyria (AIP) in an in vivo murine model. A metabolic and hepatic characterization at basal conditions as well as upon induction of a stress for acute attack will be performed. Data will be also compared to metabolic profile in AIP patients in order to provide new insights in pathogenesis of the acute attacks and to offer novel therapeutic approach for these rare disorders.
The role of extracellular matrix in non neoplastic renal pathologies
Procurement and reconditioning of marginal organs for lung transplantation. Impact of thyroid hormone on lung ischemia-reperfusion injury: development of an experimental extracorporeal lung perfusion rat model and pilot clinical trial.
Requisiti: Documented knowledge of organ procurement methods. Experience in pulmonary re-conditioning practices. Experience in animal surgical model.
Role of chaperone-mediated autophagy (CMA) in Temozolomide (TMZ) responsiveness in glioblastoma. Experiments in patient derived cells and couples of syngeneic lines (sensitive and resistant to TMZ treatment) will aim to clarify the role of CMA in the induction of cytotoxicity after TMZ. Treatments capable of modulating this process will be evaluated both in vitro and in animal models of glioblastoma with the aim of reverting Temozolomide resistance. Non-invasive optical imaging techniques will be used to follow key processes in the animal model over time.
Requisiti: Knowledge of the basic elements of molecular oncology; ability to work in a group; curiosity and originality.
Development of biomarkers for the evaluation red blood cell turnover. In subjects with chronic hemolytic anemia, red blood cell population is younger respect to healthy subjects while in subjects having not treated iron-deficiency anemia, the mean red blood cell age results to be increased due to the slowed release of reticulocytes. The project is aimed to the development of biomarkers of red blood cell age by studying proteins and metabolites related to the red cell turnover.
Requisiti: Competences in the measurement of cellular metabolites and enzymes.
Lipidomics and Calorimetric techniques to study with a multidisciplinary approach the role of membranes alterations in Diabetes (Acronym: KalOmics): The project is aimed to study the role of membranes lipid composition in platelets and secretory granules of pancreatic beta cells isolated from diabetic subjects.
Requisiti: Experience in Separative Techniques and Mass Spectrometry. Manipulation, purification and extraction of bioactive substances from biological matrices. Quantitative and statistical procedures.
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.
Requisiti: The candidate must have significant experience in Molecular Biology and bioinformatics skills in genomic data analysis. Study / work experience abroad and publications will be considered.
The most important complication in severe hemophilia A is the formation of persistent neutralizing antibodies against factor (F) VIII, called inhibitors, which render treatment ineffective. Previous data suggest that the concomitant presence of different anti-FVIII IgG subclasses is associated with an up to 3-fold higher risk of inhibitor persistence. The aim of this project is to validate the predictive value of IgG subclasses on the persistence of inhibitors. The ultimate goal of such study would thus be to identify patients likely to develop persistent inhibitors in order to tailor therapy modalities.
Requisiti: The candidate must have experiences in Molecular and Cellular Biology. He/she must have had experience of study/work abroad. Strong language skills in English is a bonus.
The study of small airway closure is the object of the present project, which consists in the development of A) an animal model in which small airway closure can be characterized with the nitrogen single breath, and visualized directly using histologic and radiographic techniques; and B) diagnostic tests for human beings able to assess airway closure in dynamic conditions.
Definition of viral markers regulating HIV and HBV persistence. Despite recent advancements in the knowledge of mechanisms of HIV and HBV persistence, complete viral genetic characterization (thanks to next-generation technologies, NGS) are still missing, as well as their correlation with disease evolution or reactivation (in the case of HBV).
Requisiti: Expertise in molecular biology, mainly in next-generation sequencing technologies.
Definition of Clinical relevance of non-tuberculous mycobacteria thanks to the application of droplet digital PCR - Pulmonary disease caused by nontuberculous mycobacteria (NTM) is increasing worldwide. Digital droplet PCR (ddPCR) is an emerging technology, potential alternative to conventional real-time PCR, able to detect low copy numbers of target DNA. The advantages of ddPCR compared to rtPCR include the fact that the microbial diagnostic procedure might become potentially more accurate and highly sensitive, which makes this new technology a potential alternative for use in the clinical diagnosis of a vast majority of microorganisms.
Requisiti: Expertise in molecular biology, mainly in ultrasensitive quantitation technologies.
Definition of bacterial determinants and gut microbiota features driving the colonization and the invasive infection in hospitalized patients - Antibiotic-resistant bacterial strains are a major health challenge, as illustrated by the recent emergence and spread of multidrug resistant gram-negative germs, especially carbapenemase-producing Klebsiella pneumoniae. However, no definite data are available regarding factors associated to the occurrence and outcome of invasive infections.
Requisiti: Expertise in molecular biology, mainly in next-generation sequencing technologies.
Techniques of Extracorporeal CO2 removal to prevent Ventilator Induced Lung Injury (VILI). ARDS (acute respiratory distress syndrome) is a specific form of acute hypoxemic respiratory failure most often requiring intensive care and invasive ventilatory support. VILI prevention is the sole treatment of proven efficacy, besides the etiologic treatment of the underlying disease. Extracorporeal removal of blood CO2 by extracorporeal circulation through membrane artificial lungs is the most effective approach to VILI prevention. Our research aims at: 1 Maximizing the amount of CO2 removed from a given blood flow rate; 2 Increase the biocompatibility of the extracorporeal system
Physiological regulatory mechanisms and development of postsurgical adverse events - Network Physiology (NP) is an emerging field of computational physiology and bioengineering 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 adverse events.
Requisiti: Expertise in biomedical signal processing and statistics
Role of sphingolipids in the mechanism of repair of damaged myelin, with focus on multiple sclerosis.
Requisiti: Knowledge of the basics of sphingolipid biochemistry. Knowledge of the techniques of cell culture.
Actigraphy based evaluation of rest-activity circadian rhythm and sleep quality in breast cancer women with BRCA mutations.
Impact of physical activity on muscular and adipose tissue homeostasis: many metabolic changes associated with physical activity can be influenced by the genetic background of each individual. The identification of genetic marker improving the benefic effects of sport activity may enable detection of the best programs of physical training that combined with caloric restriction can maximize the body weight reduction in obese subjects. This study wants to identify genetic variants (SNP, miRNA) with a positive association between metabolic activation and genetic conditioning of athletic predisposition.
Advanced techniques in digital mammography: digital breast tomosynthesis, DBT; contrast-enhanced dual energy (spectral) mammography, CESM; dual-energy non-contrast mammography
Requisiti: Basic knowledge of techniques of digital mammography
Detection and quantification of breast arterial calcifications for cardiovascular risk stratification in women: traditional methods and artificial intelligence algorithms
Requisiti: Basic knowledge of techniques of digital mammography
Neuronal and microglial exosome isolation from biological fluids of patients with neurodegenerative and demyelinating diseases, both genetically determined and sporadic, and analysis of their protein and RNA content.
Requisiti: Good knowledge of the main molecular biology methodologies, including: nucleic acid isolation, RT and digital PCR, Sanger sequencing, Next Generation Sequencing
Three-dimensional analysis of human movement in health, disease and sports
Requisiti: Basic information of the anatomy of the human locomotor system and biomechanics
Inhibition of ceramide synthesis as post conditioning therapy after myocardium infarction
Controlling sphingolipid metabolism as a disease phenotype regulator in Cystic Fibrosis
Targeting sphingolipid metabolism to reduce neurodegeneration  in Parkinson' s disease.
Age and gender factors influencing the susceptibility to severe malaria. Deadly severe malaria is due to vascular sequestration of infected red blood cell and cytokine unbalance. To investigate the contribution of gender, age and innate immunity to the severity of the disease, the effects of cytokines, sex hormones or drugs an in vitro cellular 3D model of parasite sequestration will be investigated. The results will be correlated with patient’s clinical data to propose new adjunctive treatments.
Requisiti: Basic knowledge in cell culture, immunostaining, molecular biology, immunology.
Role of exosome signaling through the epidermal growth factor family of receptors ERBB2 and ERBB4 in skeletal muscle has been controversial, but it was shown to phosphorylate α-dystrobrevin 1 (α-DB1), a component of the dystrophin associated protein complex (DAPC). This project will determine whether exosomes may affect neuregulin1 (NRG) signaling with a functional role in muscular dystrophies.
Requisiti: Knowledge of in vitro and in vivo cellular and molecular biology.
Dissecting inflammasome/cholesterol axis in antiviral immune responses. 1. Evaluation of inflammasome/cholesterol axis in primary macrophages exposed in vitro to enveloped viruses (HIV, HBV,HCV) 2. Effects of anti-HIV therapy suspension on cholesterol metabolism in primary monocyte/macrophages 3. Effects of therapy with thiazolides on NLRP3 inflammasome activity and on cholesterol metabolism in chronic HBV-infected patients
Requisiti: Knowledge of cellular and molecular immunology with omics approach
From genetics to the clinic: personalized medicine for liver disease. Aim: to identify and characterize genetic variants predisposing to hepatic fat accumulation and liver disease progression by 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 could improve patients risk stratification and identify novel therapeutic targets for NAFLD in a precision medicine perspective.
Requisiti: Experience in the field of clinical/translational research or molecular biology.
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.
Innovative and alternative therapeutical approaches for drug-resistant epilepsy
Extracorporeal supports: from isolated organ perfusion to in-vivo organ support Extracorporeal supports allow to assist or replace the function of diseased organs. The research project aims to optimize the extracorporeal support both of the isolated organ, kept alive by ex-situ persusion, and the in-vivo organ.
Dissecting the non-coding genome function T lymphocytes maturation to identify novel biomarkers and therapeutic targets for severe prematurity
Requisiti: Potential candidates should have previous experience in handling next generation sequencing (NGS) data sets (i.e. RNA-seq, ChIP seq, chromatin-RNA seq) and in programming (R, Perl, Pyton languages) and also in human T cell biology. Good communication and background in non-coding genome biology are also strongly recommended.

Enrollment

Places available: 22


Call for applications: how to do, attachment 1, Qualifications assessment and exam schedule


Application period: from 05-24-2019 to 06-24-2019
Enrolment period: from 09-23-2019 to 09-27-2019
Please note:
Allegato 1: Decreto di ampliamento dei posti e delle borse messi originariamente a concorso.