PhD program in Molecular Biomedicine

Available projects

FIXED PROJECTS / fellowships

 Fellowships are linked to the following projects
(listed in the order they are presented in the official call for applications)

Title and Supervisor Description

SB1 (senza borsa)

“Clinical utility of liquid biopsy in the treatment of endometrial cancer”

prof. Gustavo Baldassarre (CRO, Aviano)

In the last years the diagnosis and treatment of Endometrial carcinoma (EC) profoundly changed with the introduction of molecular classification and immunotherapy. On molecular point of view EC are divided in four groups on the presence/absence of alterations in POLE and TP53 genes and the presence of Microsatellite Instability (MSI). MSI EC are extremely sensitive to immunotherapy, while TP53 mutated ones are not. Based on disease stage and on molecular classification, EC patients are treated with Chemo + Radio or Chemo + Immuno-therapies.
Evaluation of DNA alterations in cfDNA could be a reliable strategy to follow EC patients during therapies and possibly help the clinicians in decision making.
The successful candidate will work in close contact with the Unit of Medical oncology to follow the clinical evolution of EC patients enrolled at CRO-Aviano. She/He will be required to learn and apply NGS-based sequences techniques to evaluate the presence of mutation and their modifications over the time, both in solid and liquid biopsies. The molecular analyses will be then related to the patients’ response to therapies to define if liquid biopsy at diagnosis and during the course of treatment could directly impact on clinical decisions and patients’ outcome.

SB2 (senza borsa)

“Development of Diagnostic Tools for cancer via the use of NGS”

prof. Claudio Tiribelli (FIF, UniTS)

 The primary objective of this project is to develop advanced diagnostic tools for cancer detection and analysis using Next-Generation Sequencing (NGS) technology. This involves creating more precise, efficient, and comprehensive diagnostic methods to identify genetic mutations biomarkers associated with various types of cancer (Lymphomas and Myelomas), thereby improving early detection, personalized treatment, and patient outcomes.


“Epigenetic regulation of the response to therapies in ovarian cancers”

prof. Gustavo Baldassarre (CRO, Aviano)

Epithelial Ovarian cancer (EOC) is still a deadly disease mainly for the appearance of recurrences resistant to first lines therapies. Gold standard treatment for EOC patients include radical surgery followed by platinum-based therapy. Introduction of maintenance treatment with PARP inhibitors, strongly improved the survival of platinum sensitive EOC. Nevertheless platinum-resistant EOC are usually cross resistant with PARP inhibitors and largely uncurable.
Resistance to chemotherapy in EOC is not associated with specific genomic alterations suggesting that epigenetic modifications could play a major role in these settings.
Using several platinum-sensitive and resistant isogenic and patient-derived models generated in the PI lab, the successful candidate will study how epigenetic modifications including histones post-translational modifications and regulation of RNA transcription, could impact on the capacity of EOC cells to survive the pressure of therapies and become resistant.
Ideally, this project will identify specific molecular candidates to be used as novel therapeutic targets that should be able to improve the efficacy of platinum-based therapies and prevent the onset of recurrent resistant disease.
To reach this objective, the candidate will learn and apply all the molecular and cellular biology techniques used in cancer research along with in vivo analyses, working in a stimulating multidisciplinary environment. 


“Exploring the biological diversity of luminal breast cancer with patient derived models

prof. Gustavo Baldassarre (CRO, Aviano)


Breast cancer is the most common cancer in women with more 55.000 cases each year only in Italy. Yet, it is not a single disease but different histotypes and molecular subtypes exist. This project aims understanding the biological diversity of Luminal Breast Cancer (LBC), the most common molecular BC subtypes. LBC might have a very favorable course or become readily resistant to treatment with hormonal therapies. LBC have a peak of recurrences two years after the original surgery but could also recur many years later. LBC could appear as indolent tumor localized to the breast but also as highly aggressive metastatic disease.
The successful candidate will learn and apply all the molecular and cellular biology techniques used in cancer research along with in vivo analyses, working in a stimulating multidisciplinary environment and will mainly use characterized patient-derived organoids (PDO) and xenografts (PDX) to understand which are the main differences in LBC at different stages of disease. Particular focus should be applied to study the emergence of resistance to targeted therapies used as standard treatment for LBC patients. 


“Interaction between SARS-CoV-2 and cellular pathways

dr. Giuditta De Lorenzo (AREA, Trieste) and prof. Marco Scocchi (DSV, UniTS)

 Severe COVID-19 is characterized by the inefficient suppression of early stages of infection followed by an exacerbated response once the virus has proliferated, resulting in hyperinflammation and cytokine storm, acute respiratory syndrome, tissue damage, multi-organ failure, with long-term effects known as Long COVID.
SARS-CoV-2 infection has been reported to compromises genome integrity by causing virus-induced DNA damage (VIDD) through the viral proteins Orf6 and NSP13, and by inhibiting DNA repair through the Nucleocapsid (N) protein. This leads to activation of proinflammatory pathways and virus-induced senescence (VIS) with autocrine/paracrine activity. Recent variants of concern have shown recurrent substitutions in Orf6, N and NSP13, and enhanced expression of Orf6 and N including the production of a novel subgenomic RNA encoding a truncated form of N.
This doctoral project aims to get a better insight into the molecular mechanisms behind VIDD and VIS in the context of neuroinflammation and also characterize the effect of the aminoacidic changes accumulated with evolution. This will help a better understanding of the endocrine and paracrine consequences of SARS-CoV-2-mediated DNA damage and pave the way for a senolytic treatment.
The candidate will perform standard molecular biology assays and will be trained for handling of virus in BSL-3, the use of fluorescence confocal microscopy and the generation of recombinant proteins. The candidate will be involved in a collaboration with ICGEB (Trieste), IGM-CNR (Milan) and the Laboratories of Genomics and Epigenomics (LAGE) and Data Engineering (LADE) in Area Science Park.


“A synaptic mechanogenetic stimulation as treatment for early infantile epileptic encephalopathy type 9

prof. Maria Passafaro (Institute of Neuroscience, Milano)
and prof. Lorenzo Cingolani (DSV, UniTS)

Mutations in the X-chromosome gene PCDH19 cause DEE9. DEE9 is characterized by early-onset epilepsy and very heterogeneous spectrum of neuropsychiatric symptoms, including intellectual disability.
PCDH19 encodes protocadherin-19 (PCDH19), an adhesion molecule of the cadherin superfamily. The adhesive properties and synaptic expression  of PCDH19 make this protein well equipped for neuronal circuit organization, as suggested by its involvement in neuronal migration, sorting and clusterin. Furthermore, PCDH19 mismatch at synapses has recently been shown to affect NCAD-dependent signaling at presynaptic terminals of mossy fibers, impairing their function. In this project will use the synaptic methanogenetic stimulation to repair the functional impairment in DEE9. This will be studied in neuronal cultures by using magneto-mechanical stimulation in combination with imaging, biochemistry and multi electrode arrays (MEA) techniques. 


“In vivo cellular fate-mapping studies to investigate the contribution of candidate genes involved in lung regeneration and pulmonary fibrosis

prof. Marco Confalonieri (DSM, UniTS)

This research project aims to assess the therapeutic relevance of selected targets in curing Idiopathic Pulmonary Fibrosis, focusing specifically on the effects of these targets on alveolar epithelial type II (ATII) cells. The project will utilize both in vitro techniques, using primary mouse ATII cells, and in vivo techniques with transgenic (Tg) mouse models that allow ATII-restricted gene manipulation and lineage tracing. The efficacy of the selected therapeutic targets will be examined at cellular and molecular levels both in vitro and in vivo.  First, the selected targets will be functionally assessed for their ability in restoring ATII to ATI trans-differentiation in diseased ATII cells through gene manipulation in vitro. Second, to gain a deeper understanding about their role in combating IPF phenotype in vivo, the relevance of the selected targets will be further assessed in vivo by leveraging a mouse model of ATII-restricted expression of CRISPR-associated protein 9 (CAS9) endonuclease challenged either by bleomycin administration or pneumonectomy (PNX). This model will enable the ATII-restricted knockout of selected molecular targets and consequently assess the impact on both lung repair and compensatory lung growth. This research will lead to the identification and validation of new druggable targets for the treatment of Idiopathic Pulmonary Fibrosis.


“Development of precise gene editing strategies to cure inherited cardiomyopathies

prof. Mauro Giacca (DSM, UniTS)

The project aims to develop effective protocols for the precise correction of the DNA mutations that cause genetically inherited cardiomyopathies. These are relatively frequent cardiac disease conditions, with a prevalence of 1:500 individuals in the general population for hypertrophic cardiomyopathy (HCM). The PhD student will develop lipid nanoparticles that specifically target cardiomyocytes and methods that induce homology directed repair using an exogenously administered normal DNA sequence, used as a template for genetic correction. The developed methods will be tested in parallel in human iPS cell-derived cardiomyocytes from patients with myosin binding protein C (MYBPC3) mutations (the most frequently affected gene in HCM) and in a mouse model with a humanised mutation in the same gene. 


“Impact of the tissue microenvironment on oncogenic signaling during tumor initiation and evolution

prof. Giannino Del Sal (ICGEB, UniTS)

Research activity of the Cancer Cell Signaling group aims at understanding the interplay between tissue microenvironment and oncogenic signaling in cancer, with the ultimate goal to develop preventive and therapeutic strategies.
Tumors evolve through genetic and epigenetic alterations that occur in cells over time, and are selected by tissue microenvironmental alterations allowing survival and expansion of best-adapted clones. However the mechanism governing this clonal dynamic, especially during the initial phases of tumorigenesis and also in the development of metastases, are still poorly understood.
Recent genome sequencing studies unveiled that, in many tissues, cell clones bearing oncogenic mutations accumulate with age well before histological alterations. However, not all the clones evolve into cancer, suggesting that their oncogenic potential is influenced by microenvironmental and epigenetic factors.
In this context, the group is developing a research line aimed to investigate how aging-associated microenvironmental alterations known to increase cancer risk, such as inflammation and fibrosis, impact on tumor initiation and evolution. To this aim, the group integrates the use of state-of-the-art in vivo (Drosophila, mice), ex vivo and cellular models, with advanced imaging, multi-omics molecular technologies and bioinformatics approaches. 


“Prolyl isomerase PIN1 inhibition as a strategy against aggressive tumours

prof. Giannino Del Sal (ICGEB, UniTS)



“Novel strategies to fight multi-resistant bacterial pathogens

prof. Paola Cescutti (DSV, UniTS)

Multi-drug resistance (MDR) in bacteria have reached worrisome levels. Treatment of MDR bacterial infections is very often unsuccessful, because of the lack of efficacious antibiotics and has become a major public health problem. The most dangerous MDR bacteria belong to the ESKAPE group which includes Klebsiella pneumoniae. This situation is so alarming that CDC and WHO indicated some of these species as “urgent threats” or “critical priority” pathogens.
This project aims at using phage-derived compounds to combat human infections caused by MDR Klebsiella pneumoniae. The idea is to exploit the specificity of bacteriophage endoglycosidases, hydrolases that have the pathogen capsular polysaccharide as a substrate, to guide drug-carriers to the target microorganism selectively, without interfering with the host microbiome. The endoglycosidase will be anchored on the outer surface of a liposome which will carry inside a bactericidal compound. The endoglycosidase, by degrading the capsule, will allow the liposome to reach and fuse with the outer membrane of the bacterium, pouring its antibacterial content into the periplasm. As bactericidal compounds available antibiotics, like vancomycin, and spanin or disruptin of phage origin will be tested. This project is intended to be a proof of principle that such an approach can be used as an innovative and effective tool against MDR bacteria.


“Role of the chromatin architectural factor HMGA1 in modulating the secretome of breast cancer cells

prof. Guidalberto Manfioletti (DSV, UniTS)

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of tumor. Patients with TNBC have a relatively poorer outcome compared to those affected by other BC subtypes, because of the typically aggressive cancer behavior and the absence of recognized targets for specific therapies.
The project will exploit the architectural transcription factor HMGA1, a master regulator in TNBC-related key processes, able to modulate chromatin structure and function, reshaping the gene expression program leading to EMT and stemness, cell migration and invasion, anchorage independent growth, metastasis formation in vivo, and chemoresistance.
Cellular models will be exploited to characterize the HMGA1-dependent miRNA content of cancer cell-derived extracelluar vesicles. The expression of selected miRNA will be subsequently evaluated in blood patients’ samples as a possible predictive biomarker and prognostic factor.
The aim is to discover easily-detectable and conceivable biomarkers to predict the TNBC prognosis, to anticipate the disease evolution and to envisage the impact of the anti-cancer therapies while on treatment and thereafter. 



“Dissecting the oxinflammatory mechanisms involved in Rett Syndrome pre-symptomatic/ symptomatic switch: focus on mitochondria and inflammasome activation

prof. Gabriele Baj (DSV, UniTS)

Rett syndrome (RTT) is a genetic neurodevelopmental disorder characterized by progressive regression of mental and psychomotor development (symptomatic phase).Evidence indicates that metabolic abnormalities including mitochondrial dysfunction, aberrant redox homeostasis and subclinical inflammation significantly contribute to RTT. While many abnormal molecular and cellular aspects of RTT have been fairly delineated in its symptomatic phase, what happens before the onset of symptoms still remains unknown. However, the peculiar pathogenic development of RTT characterized by a relatively slow transition to the symptomatic stage offers a precious time window of opportunity for early diagnosis and intervention. Based on these premises, we intend to identify the chain of molecular events involved in the enigmatic switch from presymptomatic to symptomatic stage of RTT. We plan to take advantage of suitable in vivo, in vitro and ex vivo models of RTT, such as Mecp2-null mouse model, RTT patient iPSCs and serum samples.We will evaluate KO mice primary cells and human iPSCs from RTT patients monitoring overtime the mitochondrial/inflammasome hallmarks related to the presymptomatic/symptomatic switch. The accomplishment of this project would help to furthering the understanding of RTT pathophysiology.


“Dissection of cancer stemness and therapy resistance by functional genomics

prof. Stefan Schoeftner (DSV, UniTS)

Epithelial ovarian cancer (EOC) is the most lethal gynaecological cancer with > 60.000 new cases per year in the US and EU and single therapy that is beneficial for all EOC patients is currently not available. Preliminary data show that the self-renewal transcription factor OCT4 enhance EOC aggressiveness by programming a tumor promoting microenvironment. In this context OCT4 is tightly regulated by a derivative pseudogene lncRNA that deposits epigenetic silencing complexes to the OCT4 promoter using an unprecedented epigenetic mechanism, thus impinging on ovarian cancer aggressiveness and patient survival. This highlights the relevance of a tight regulation of OCT4 dependent cancer pathways to define the tumor microenvironment (TME) in EOC.
In the current project we will  investigate how OCT4 dependent gene expression signatures and the epigenomic landscape program a tumor-promoting TME. In addition the mechanism by which the human OCT4 pseudogene 3 lncRNA (hOCT4P3) targets silencing complexes to the OCT4 promotor and alternative target genes across that epithelial ovarian cancer genome will be investigated.
The project is based on a functional genomics approach including transcritomics and epigenomics, and the application of a wide range of  bioinformatics analyses. 


“Investigating HPCAL4 as a Therapeutic Target for Episodic Ataxia Type 2 and Epileptic Encephalopathy 42

prof. Lorenzo Cingolani (DSV, UniTS)

The project explores the potential of the unknown ‘Tdark’ gene HPCAL4 for developing gene therapies for ataxia and epileptic encephalopathy. The focus is on deciphering how HPCAL4 regulates CACNA1A, a pivotal calcium channel implicated in various brain disorders. Through cutting-edge techniques (super-resolution imaging, electrophysiology and optogenetics), you will delve into the intricate workings of nerve cell communication.
Previous experience in electrophysiology is desirable. The ability to thrive in an international and competitive research environment is essential.
Join a dynamic research team driven by passion and curiosity for science. Benefit from access to state-of-the-art facilities and collaboration opportunities across Europe with renowned experts in the field. With a commitment to fostering diversity and inclusion, we welcome applicants from all backgrounds.
The position is funded by the Cariplo-Telethon alliance, supporting research on Tdark genes (genes with unknown functions in rare diseases). Our laboratory adopts an integrative approach, combining molecular, imaging and electrophysiological techniques in in vitro and in vivo models of neurological disorders
(Thalhammer et al., 2017 Cell Rep 20, 333-343; Ferrante et al., 2021 Cell Rep 35 109248, Jaudon et al., 2022 Mol Ther Nucleic Acids 29 462-480, Moretto et al. 2023 Elife 12, Jaudon and Cingolani, 2024 Trends Cell Biol.). 


“ICGEB position


One (1) position available to work in one of the research groups at ICGEB.
For more infromation, please visit the Scientific Faculty Research pages at the following link:


“UniTS position"


This fellowship can be linked to any one of the flexible projects described at the bottom of this table (see below)




“Development of precision oncology approaches for women cancers"

prof. Barabra Belletti (CRO, Aviano)

The project aims to identify new therapeutic targets for the treatment of patients with advanced/metastatic breast or gynecological cancers.
It involves a first phase of genomic analyzes on samples collected at the Aviano IRCCS CRO, using innovative NGS technologies to highlight alterations associated with progression. Subsequently, the identified alterations will be targeted using both genetic and pharmacological approaches, also in patient-derived models (PDO and PDX). 


“ICGEB position

One (1) position reserved for candidates graduated from foreign universities to work in one of the research groups at ICGEB.
For more infromation, please visit the Scientific Faculty Research pages at the following link:


"FIF positions"


Two (2) positions reserved for citizens of the Philippines recipient of a fellowship funded by the Philippine Council for Health Research and Development (PCHRD) to conduct research at the Italian Liver Foundation (FIF). 





Fellowship FSE+15 can be linked to any one of the following projects

(listed in alphabetical order by supervisor's name)

Title and Supervisor Description

"Investigation of endothelial cells for the improvement of ovarian tissue autotransplantation technology"

prof. Roberta Bulla (DSV, UniTS)

Premature ovarian failure is associated with childhood cancer treatment. Ovarian tissue cryopreservation followed by transplantation is the only available option for prepubertal girls who have survived cancer. Revascularization is one of the limiting factors for successful ovarian tissue transplantation. The aim of this project is to develop a tissue-engineered product (TEP) to improve the success rate of autologous ovarian transplantation, reduce the ischemic window and improve recovery and survival. To this end, the following objectives are proposed
1. Inosculation selected matrices, possibly commercial matrices used clinically for wound healing, with autologous endothelial cells isolated from human skin or alternatively with the stromal vascularized fraction (SVF), a heterogeneous collection of cells contained in adipose tissue
2.Evaluate the ability of this vascularized TEP to improve implantation and survival of ovarian tissue sections before and after cryopreservation
3. investigate the innate immune response to ovarian tissue damage to determine markers of ovarian ischemia that may be useful for understanding the mechanisms leading to ovarian ischemia after cryopreservation.

"Understanding astroglia contribution to seizure propensity in Rett syndrome "

prof. Francesca Cesca (DSV, UniTS)

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl-CpG Binding Protein 2 (MeCP2) gene. About 60% of RTT patients show epileptic seizures, however, epileptogenesis in RTT is still poorly understood. We are interested in understanding the contribution of astrocytes to seizure propensity in RTT.
This is a collaborative project between Prof. Cesca’s group at UniTS and Dr. Falcone’s group at SISSA. We will use in vitro co-cultures of human astroglia, derived from RTT patients and healthy controls, and primary rodent neurons to study how RTT astroglia induce hyperexcitability, through live Ca2+ imaging and multi-electrode array experiments. We will also perform xenotransplants of human astroglia precursors in the brain of immunodepressed mice, to study the impact of RTT astroglia on cognition, through behavioral tests, and on seizure propensity, by injecting the convulsant drug pentylenetetrazol. Focusing on human astrocytes is crucial to set the stage for translational studies.

"Mechanisms of inactivation of the tumor suppressor DAB2IP in cancer"

prof. Licio Collavin (DSV, UniTS)

The RasGAP protein DAB2IP negatively modulates multiple oncogenic pathways, such as Ras/RTK, TNF/NF-kB, PI3K/AKT, and WNT/beta-catenin, thus acting as a bona fide tumor suppressor. DAB2IP expression is often reduced by gene methylation in tumors. However, in many cancers the gene is not silenced, and its functions is inhibited by other mechanisms (Bellazzo, 2016). For instance, we discovered that DAB2IP can be disabled by interaction with mutant forms of the p53 protein, with crucial implications for cancer aggressiveness in response to inflammation and to Insulin (Di Minin, 2014; Valentino, 2017). We also found that DAB2IP protein levels can be reduced both in cancer cells and in non-cancer cells of the tumor stroma, suggesting the existence of a cell non-autonomous mechanism of DAB2IP inactivation, that may be very important for cancer progression. This project has two main objectives: 1) to further characterize the mechanisms of DAB2IP inactivation in cancer, study their functional impact, and evaluate their diagnostic and prognostic potential; 2) to explore approaches aimed to restore DAB2IP functions in cancer cells as innovative cancer therapeutics.

"HCC therapeutics"

prof. Gabriele Grassi (DSM, UniTS)

Hepatocellular carcinoma (HCC), an important cause of global death, develops in 90% of cases in the context of hepatic fibrosis (HF). HCC and HF represent a significant burden on healthcare in terms of costs and personnel commitment.
We propose a novel therapeutic strategy based on the inhibition of the pro-HCC effects of the precancerous HF liver. The molecules used will be deubiquitinase inhibitors (2C and derivatives) developed by us. The drugs will be tested in human hepatic stellate (HSC) cell lines/primary HSCs, the major drivers of HF (collaboration with Prof Weiskirchen (Universitätsklinikum Aachen, Germany) evaluating the phenotypic/molecular effects (focus on E2F1). Since the viscoelasticity of the culture surface influences the phenotype of HSCs, we will also generate culture surfaces that mimic the viscoelasticity of the pathological liver (collaboration with Prof M Grassi, UNITS), to generate data more predictive for in vivo tests. Cellular models of steatosis/liver inflammation (collaboration with Prof Pastorin, National University of Singapore), organoids (collaboration with Prof Rizzolio, CRO, Aviano) and in vivo tests (Prof Nhung Truong, University of Science, Ho Chi Minh City) will be also undertaken to study drugs effects/mechanisms of action. The candidate will therefore have the possibility of being hosted in the collaborating centers.

"Identification of cancer-derived factors modulating the tumor ecosystem."

prof. Fiamma Mantovani (DSV, UniTS)

 Tumors behave as complex and dynamic ecosystems where cancer cells interact with cellular and non-cellular stromal and immune components. Alterations of the tumor microenvironment (TME) affect cancer cells’ fate, metastatic capability and therapy response, yet the mechanisms and cell types at play remain understudied. Our lab identifies proteins and non-coding RNAs acting either in a cell-autonomous or in a paracrine fashion to reshape primary and metastatic tumor niches, generating permissive environments supporting tumor growth, immune evasion, metastatic colonization and therapy resistance. These factors may represent biomarkers and/or actionable targets for improving treatment of aggressive tumors. We focus on candidate factors (proteins and miRNAs) produced by aggressive tumor cells downstream of oncogenic pathways in response to cancer-related stimuli (including hypoxia, mechanostimulation and inflammatory cues), that impinge on the communication between tumor, stromal and immune-inflammatory cells. The PhD candidate will evaluate the functional relevance and the mechanism of action of selected factors by analyzing the impact of their genetic/pharmacologic modulation on tumor-TME crosstalk using in vivo, ex-vivo and in vitro experimental models of breast cancer and other tumors and metastasis. Moreover, validated factors may be tested for their potential as circulating biomarkers of metastatic disease and predictors of response to treatments.

"Exploiting novel dissipative extracellular matrix mimics to develop fundamental knowledge in CARTIlage REGENeration - CARTIREGEN"

prof. Pasquale Sacco (DSV, UniTS)

Cutting-edge biomaterials that mimic the microenvironment of natural articular cartilage (AC) are urgently needed to provide fundamental insights into AC regeneration. Indeed, AC-associated disorders still remain one of the leading causes of disability and represent a tremendous socioeconomic burden worldwide. Current biomaterials used to mimic the AC microenvironment to understand cell biology suffer from their purely elastic nature. Yet, AC represents a physiological damper of mechanical stresses. Although it has recently emerged as a novel regulator of cellular responses, the contribution of material dissipation to guiding cell-fate decisions is still in its infancy. Therefore, in the first instance the project aims to fabricate AC-inspired extracellular matrix mimics in the form of hydrogels showing tunable dissipation rate. To achieve this milestone, the PhD student will leverage recent discoveries in the Supervisor’s Lab. The second theme of the project aims to test the chondroinductive properties of the AC mimics. Chondrocytes biology as well as mesenchymal stem cells differentiation will be investigated in vitro using both 2D and 3D settings. In addition to achieving these major objectives, CARTIREGEN will also generate different intermediate goals, providing basic knowledge and pivotal elements of novelty to move forward AC tissue engineering field beyond the current state-of-the-art.

 "Combating resistant intracellular infections by Acinetobcter baumanii"

prof. Marco Scocchi (DSV, UniTS)

Acinetobacter baumannii is an opportunistic pathogen listed by theWHO in the ESKAPE group causing serious concern for their high level of antibiotic resistance. It has been recently shown that to survive and multiply eukaryotic phagocytic cells, further complicating antibiotic treatment efforts.
Proline-rich antimicrobial peptides (PrAMPs) have emerged as promising alternatives to currently un-effective antibiotics due to their potent activity against resistant Ab and low cytotoxicity to human cells. This doctoral project aims to investigate cellular interaction of PrAMPs, the route and rate of internalization and final cellular destination. This acquired knowledge will then serve to apply PrAMPs for the treatment of intra-cellular infection by Ab and assess their potential to completely eradicate it, and will require the development of a powerful and informative infection model comprising the use of mixed bacteria/cell co-cultures. This will pave the way for the development of sustainable and targeted new interventions to combat persistent bacterial infections in host cells, and in particular provide crucial data on their potential as an effective treatment against intracellular Ab, addressing a significant gap in current therapeutic strategies.
The candidate will apply methods of biochemistry and cell biology, be trained in the use of fluorescence confocal microscopy and flow cytometry and will become proficient in applied microbiological skills required to handle pathogenic microbial cultures. 


 "Studies on the functions and modes of action of primate cathelicidins as leads for the design of multifunctional antiinfective agents."

prof. Alessandro Tossi (DSV, UniTS)

Antimicrobial peptides (AMPs) are a first line of defence against infections and an important component of innate immunity. Among AMPs, the cathelicidin family has been extensively studied for its pleotropic effects in immunity, in both physiological and pathological environments.
The proposed project investigates the molecular features underlying the behaviour of the human cathelicidin LL-37 in comparison to other primate cathelicidins, as well as their structural analogues, using biophysical, biochemical and biopharmacological techniques. This multidisciplinary approach includes the design, synthesis and modification of cathelicidins biophysical, microbiological and biopharmacological studies.
These will include studies in A) eukaryotic cells to i) evaluate cytotoxicity; ii) investigate the mechanism of action with a focus on membrane-mediated effects; iii) analyse the effects on the purinergic receptor P2X71 in modulating pyroptosis in M1 macrophages; and B) bacteria to iv) investigate its antibiotic activities (MIC, MBC) and  iv) the mechanism of action on microbial and model membranes.
The PhD student will acquire advanced preparation (design, peptide synthesis and functionalization), analytical (purification and mass spectroscopy), biophysical (CD, ITC, SP) and biopharmacological knowledge (microbiology, cell biology, flow cytometry techniques). The doctoral project will be carried out both at the DSV and at the IC-CNR (Basovizza), as it is a cross-sectional project.



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"Molecular basis of synaptic plasticity determined by calcium channels in primary neurons"

prof. Eugenio Fornasiero (DSV, UniTS) and Prof. Lorenzo Cingolani (DSV, UniTS) with CyNexo S.r.l.

This project aims to investigate some of the fundamental plastic properties of neurons, the cells responsible for neurotransmitter release in the brain which are at the basis of complex behavioral functions such as memory and cognition. Specifically, the student will learn a range of advanced neurophysiological technologies and use them to elucidate the relationship between the precise subcellular localization of calcium channels at presynaptic sites and how they can be recruited by synaptic activity. The work will be developed in collaboration between UniTS, the University Medical Center Göttingen (Germany), which will be involved in advanced microscopy experiments, and CyNexo, a company excelling in mechatronic engineering, which will help develop a compact device for stimulating and reading neuronal activity. The main goals of this work are: 1) define the distribution of channels in different activity regimes using tailored and precise labeling and high-resolution microscopy; 2) clarify the impact of recruited channels on synaptic efficiency using calcium imaging and optogenetics; and 3) evaluate the role of re-localization in human pathology by studying mutant channels from patients with disorders associated with brain diseases. Overall, the project is expected to provide a new paradigm for understanding how presynaptic plasticity is regulated. 

 "New non-invasive molecular biomarkers for the early diagnosis of pleural mesothelioma"

Prof. Federica Tramer (DSV, UniTS) with AB ANALITICA S.r.l.

 Malignant mesothelioma (MM) is a difficult tumor to diagnose and several serum biomarkers have been investigated for the non-invasive early detection of MM, but none has achieved a sufficient combination of sensitivity and specificity.
The aim of this project is to identify new non-invasive circulating biomarkers to create a battery of composite biomarkers that characterize the profile of bile pigments (biliverdin and bilirubin, BV and BR) in the serum of asbestos-exposed individuals since these pigments reflect changes in iron metabolism, which plays an important role in the development of MM and other tumors. The University of Trieste - Department of Life Sciences will receive the clinical samples (serum/plasma) from the University of Ljubljana for bile pigments analyses using validated ultrasensitive methods. The obtained data will be utilized to search any association with data obtained at University of Ljubljana by analyzing novel genes/SNPs and/or with already published SNP data. The candidate in collaboration with the company (AB ANALITICA) will play a key role in the validation of molecular markers using Next Generation Sequencing (NGS) technology.