ATENEO CN - non associata a curriculum
- CN3, Centro Nazionale di Ricerca Sviluppo di terapia genica e farmaci con tecnologia a RNA, Spoke 3 - Neurodegenerative Targeting RNA-binding proteins to control neurodegenerative and neurodevelopmental diseases
Ente finanziatore: Sapienza Università degli Studi di Roma
Competenze richieste: nessuna competenza specifica richiesta
- CN3, Centro Nazionale di Ricerca Sviluppo di terapia genica e farmaci con tecnologia a RNA, Spoke 3 - Neurodegenerative Targeting RNA-binding proteins to control neurodegenerative and neurodevelopmental diseases
Funded by: Sapienza Università degli Studi di Roma
Required skills: no specific skill required
Descrizione: Due to their intrinsic properties, RNA molecules combine the dual function of tethering proteins as well as other nucleic acids. RNA-RNA and RNA-protein interactions allow the nucleation of different membrane-less compartments where the most essential cellular processes occur, such as transcription, processing, translation and intracellular transport. The main goal of our project is to be able to control the structure and function of specific ribonucleoprotein (RNP) complexes by targeting the RNA-RNA and RNA-proteins interactions and to understand how they contribute to gene expression control, to RNP assembly and function, and intracellular trafficking in neurons and muscles. To this aim, we will use integrated experimental and computational approaches. In neuro-degenerative diseases such as ALS, Alzheimer and many others, a causative link has been found between the pathology and the conversion of RNP granules into solid-like aggregates indicating that, by trapping crucial RNAs and proteins, they can lead to the dysfunction of many cellular processes. The ability to control the aggregation of these nuclear and cytoplasmic assemblies, by acting at the level of RNA or RNA-binding protein components, represents highly innovative research. We expect that these studies will strongly increase our understanding of basic molecular processes controlled by RNA molecules and RNA-binding proteins and should also constitute a largely unexplored territory for the development of novel therapeutics and diagnostics.
Description: Due to their intrinsic properties, RNA molecules combine the dual function of tethering proteins as well as other nucleic acids. RNA-RNA and RNA-protein interactions allow the nucleation of different membrane-less compartments where the most essential cellular processes occur, such as transcription, processing, translation and intracellular transport. The main goal of our project is to be able to control the structure and function of specific ribonucleoprotein (RNP) complexes by targeting the RNA-RNA and RNA-proteins interactions and to understand how they contribute to gene expression control, to RNP assembly and function, and intracellular trafficking in neurons and muscles. To this aim, we will use integrated experimental and computational approaches. In neuro-degenerative diseases such as ALS, Alzheimer and many others, a causative link has been found between the pathology and the conversion of RNP granules into solid-like aggregates indicating that, by trapping crucial RNAs and proteins, they can lead to the dysfunction of many cellular processes. The ability to control the aggregation of these nuclear and cytoplasmic assemblies, by acting at the level of RNA or RNA-binding protein components, represents highly innovative research. We expect that these studies will strongly increase our understanding of basic molecular processes controlled by RNA molecules and RNA-binding proteins and should also constitute a largely unexplored territory for the development of novel therapeutics and diagnostics.
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ATENEO CN - non associata a curriculum
- CN3, Centro Nazionale di Ricerca Sviluppo di terapia genica e farmaci con tecnologia a RNA, Spoke 2 - Cancer Small synthetic RNA molecules for the development of innovative anti-cancer immunotherapeutic and epigenetic approaches
Ente finanziatore: Sapienza Università degli Studi di Roma
Competenze richieste: nessuna competenza specifica richiesta
- CN3, Centro Nazionale di Ricerca Sviluppo di terapia genica e farmaci con tecnologia a RNA, Spoke 2 - Cancer Small synthetic RNA molecules for the development of innovative anti-cancer immunotherapeutic and epigenetic approaches
Funded by: Sapienza Università degli Studi di Roma
Required skills: no specific skill required
Descrizione: Accumulating evidence indicates a strong correlation between aberrant RNA modifications and cancer initiation, progression, and drug resistance. Therefore, RNA-modifying enzymes are becoming important anticancer drug targets. One of the most relevant RNA modifications in cancer is the N6-methyladenosine (m6A). m6A is the most abundant internal modification in mRNA and it is reversible and dynamic. m6A is mainly installed by the nuclear complex composed of two methyltransferase-like proteins, METTL3 and METTL14, and can be removed by the ALKBH5 and FTO demethylases. Interestingly, in some types of cancer both writers and erasers can play oncogenic roles. Furthermore, in different tumors mis regulation or new oncogenic activities can be acquired by their altered subcellular localization. Chronic Myeloid leukaemia (CML) is a cancer characterized by the clonal expansion of myeloid cells. CML is associated in about 95% of patients with the production of the oncogenic BCL-ABL1 fusion gene. The use ABL1 tyrosine kinase inhibitors (TKI) made CML a clinically manageable and a cured disease. However, in many cases, treatment with TKIs is not curative BCR-ABL1-independent pathways play important roles in TKI resistance and persistence of leukemic stem cells. We will investigate the oncogenic roles of the METTL3 methyltransferase and the FTO demethylase in CML and the impact of their selective inhibition by small molecules.
We aim at: 1) characterize the molecular function of FTO and METTL3 inhibitors in TKI-sensitive and -resistant CML cells to identify new relevant pathways; 2) test the therapeutic efficacy in preclinical in vitro models for CML; and 3) test inhibition of METTL3 and FTO alone or in combination with drugs already use in the clinic to prevent and/or overcome TKI resistance.
Description: Accumulating evidence indicates a strong correlation between aberrant RNA modifications and cancer initiation, progression, and drug resistance. Therefore, RNA-modifying enzymes are becoming important anticancer drug targets. One of the most relevant RNA modifications in cancer is the N6-methyladenosine (m6A). m6A is the most abundant internal modification in mRNA and it is reversible and dynamic. m6A is mainly installed by the nuclear complex composed of two methyltransferase-like proteins, METTL3 and METTL14, and can be removed by the ALKBH5 and FTO demethylases. Interestingly, in some types of cancer both writers and erasers can play oncogenic roles. Furthermore, in different tumors mis regulation or new oncogenic activities can be acquired by their altered subcellular localization. Chronic Myeloid leukaemia (CML) is a cancer characterized by the clonal expansion of myeloid cells. CML is associated in about 95% of patients with the production of the oncogenic BCL-ABL1 fusion gene. The use ABL1 tyrosine kinase inhibitors (TKI) made CML a clinically manageable and a cured disease. However, in many cases, treatment with TKIs is not curative BCR-ABL1-independent pathways play important roles in TKI resistance and persistence of leukemic stem cells. We will investigate the oncogenic roles of the METTL3 methyltransferase and the FTO demethylase in CML and the impact of their selective inhibition by small molecules.
We aim at: 1) characterize the molecular function of FTO and METTL3 inhibitors in TKI-sensitive and -resistant CML cells to identify new relevant pathways; 2) test the therapeutic efficacy in preclinical in vitro models for CML; and 3) test inhibition of METTL3 and FTO alone or in combination with drugs already use in the clinic to prevent and/or overcome TKI resistance.
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ATENEO CN - non associata a curriculum
- CN2, Centro Nazionale di Ricerca Tecnologie dell’agricoltura (Agritech), Spoke 7 - Integrated models for the development of marginal areas to promote multifunctional production systems enhancing agroecological and socio-economic sustainability Integrated models for the development of marginal areas to promote multifunctional production systems enhancing agroecological and socio-economic sustainability
Ente finanziatore: Sapienza Università degli Studi di Roma
Competenze richieste: nessuna competenza specifica richiesta
- CN2, Centro Nazionale di Ricerca Tecnologie dell’agricoltura (Agritech), Spoke 7 - Integrated models for the development of marginal areas to promote multifunctional production systems enhancing agroecological and socio-economic sustainability Integrated models for the development of marginal areas to promote multifunctional production systems enhancing agroecological and socio-economic sustainability
Funded by: Sapienza Università degli Studi di Roma
Required skills: no specific skill required
Descrizione: The aim of this PhD project is to provide experimental evidence supporting the use of natural, bioactive compounds such as (but not limited to) essential oils on crop growth and yield. Selected compounds will be extracted from plants that can be grown by farmers in patches of non-cultivated land (“marginal areas”). These compounds will be tested for their biological activities on different plants belonging to the Brassicaceae family: the model plant Arabidopsis thaliana and the crop Brassica sylvestris. Several growth traits will be evaluated, but we will mainly focus on flower opening, as this is a key biotechnological trait for the Brassicaceae family. The molecular and physiological basis of the plant response to these compounds will be also evaluated in detail, using a genetic and whole genome approach. This will lead to the identification of the molecular networks responsible for the effect of a given bioactive compound.
In summary, by combining field and laboratory data, the results obtained within this research project will provide farmers with validated protocols to optimize crop growth and yield under a sustainable farming regimen.
Description: The aim of this PhD project is to provide experimental evidence supporting the use of natural, bioactive compounds such as (but not limited to) essential oils on crop growth and yield. Selected compounds will be extracted from plants that can be grown by farmers in patches of non-cultivated land (“marginal areas”). These compounds will be tested for their biological activities on different plants belonging to the Brassicaceae family: the model plant Arabidopsis thaliana and the crop Brassica sylvestris. Several growth traits will be evaluated, but we will mainly focus on flower opening, as this is a key biotechnological trait for the Brassicaceae family. The molecular and physiological basis of the plant response to these compounds will be also evaluated in detail, using a genetic and whole genome approach. This will lead to the identification of the molecular networks responsible for the effect of a given bioactive compound.
In summary, by combining field and laboratory data, the results obtained within this research project will provide farmers with validated protocols to optimize crop growth and yield under a sustainable farming regimen.
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PNRR351 - non associata a curriculum
- Approcci sperimentali innovativi nella ricerca biomolecolare e genetica
Competenze richieste: nessuna competenza specifica richiesta
- Innovative experimental approaches in genetic and biomolecular research
Required skills: no specific skill required
Descrizione: La tematica è associata ai progetti 1-16 nella lista dei progetti disponibili pubblicata nel sito web del dottorato
Description: The topic is associated with projects 1-16 in the list of available projects published on the PhD website
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PNRR352 - non associata a curriculum
- Mutabilità del DNA ripetitivo in malattie associate all'invecchiamento
Competenze richieste: nessuna competenza specifica richiesta
- Investigating the basis of repetitive DNA mutagenesis in aging-associated diseases
Required skills: no specific skill required
Descrizione: Nell'ultimo decennio sono stati compiuti grandi passi avanti nella genomica umana. Ci stiamo avvicinando a una mappatura completa dello stato genetico ed epigenetico del genoma umano. Tuttavia, la comprensione dei cambiamenti associati alla diversità genetica, il modo in cui il genoma e l'epigenoma variano tra i vari tessuti e tipi di cellule e, soprattutto, il collegamento con gli stati patologici rimangono elusivi. Utilizzando nuovi metodi biochimici, tra cui CUT&TAG e sequenziamento di terza generazione, questo progetto di dottorato si propone di esplorare e caratterizzare i cambiamenti nelle caratteristiche della cromatina nel genoma umano in condizioni biomimetiche di stress endogeno e citotossicità. In particolare, il lavoro mira a (1) identificare nuovi polimorfismi e segnali mutazionali, (2) indagare come questi influenzino l'epigenoma e il comportamento della cromatina e (3) trovare un'associazione causale con le malattie umane. A tal fine, le mutazioni saranno caratterizzate utilizzando i più recenti assemblaggi genomici ed esplorando la loro rilevanza confrontando diverse condizioni sperimentali, in particolare quelle di danno e di stress cellulare endogeno. Il progetto comprende sia componenti di laboratorio che analisi bioinformatiche.
Description: The last decade has seen great strides being made in human genomics. We are moving toward comprehensively mapping the genetic and epigenetic status of the human genome. However, understanding changes associated with individual polymorphism, how the genome and epigenome vary across tissues and cell types and especially, the connection with pathological states remains elusive. Using novel biochemical methods including CUT&TAG and third-generation sequencing, this Ph.D. project proposes to explore and characterize changes in chromatin features across the human genome under conditions biomimetic of endogenous stress and cytotoxicity. Specifically, the work aims to (1) identify novel polymorphisms and mutational signatures, (2) investigate how they affect the epigenome and chromatin behavior, and (3) find a causative association with human diseases. To this end, changes will be characterized using the latest assembly and explore their relevance comparing across different experimental conditions, especially those of damage and endogenous cellular stress. The project includes both wet-lab component and bioinformatic analyses.
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PNRR352 - non associata a curriculum
- Identificazione di mutazioni somatiche utili a rilevare la presenza di tumori ginecologici
endometriali e ovarici durante Pap test di routine
Competenze richieste: nessuna competenza specifica richiesta
- Early detection of somatic mutations associated with the presence of endometrial and ovarian gynecological tumors during routine Pap smears
Required skills: no specific skill required
Descrizione: Epithelial ovarian cancer (OC) is the leading cause of gynecologic cancer-related deaths in women, primarily because most patients present with advanced-stage disease. Moreover, in the last 20 years, the incidence rate of another gynecologic cancer, endometrial cancer (EC), has increased by 125% worldwide and despite improved diagnosis and treatment methods, up to 30% of EC patients are primarily diagnosed with stage III or IV EC and have poor outcomes. Cervical cancer, on the other hand, is much less frequent in developed countries thanks to the wide availability and effectiveness of screening with the Pap test (Papanicolau test) patients allowing for early diagnosis and surgical therapy. Unlike cervical cancer, for OC and EC there are no primary (vaccination) or secondary (population screening) prevention tools that allow for an early diagnosis and timely therapeutic intervention. Also, the identification of endometrial and ovarian cancer cells through microscopy examination of the specimen often fails to discriminate such cells from benign conditions or from cervical tumors.
Recently, it has been shown that malignant cells exfoliate from the ovaries and may be detected in Pap specimens, routinely collected through cervical cancer screening. By analyzing the cells shed from the cervix, the health state of other female reproductive organs, such as the ovaries, fallopian tubes and endometrium can be also evaluated. Endocervical DNA or intrauterine DNA can be obtained through vaginal tampons, intrauterine lavage, Pap smear, and Tao Brush to determine the presence of malignant tumor cells in the reproductive tract. Circulating tumor DNA is a type of cell-free DNA that accounts for a small part of circulating cell-free DNA. It is usually released from tumor tissues in vivo and harbors tumor-specific DNA mutations, which can be detected using massive parallel sequencing (NGS).
In this project, we will develop NGS-based tumor DNA screening tests on cervical specimens, with the potential to increase the chances of early detection of endometrial and ovarian cancers in asymptomatic women. The purpose of the new test is to facilitate the diagnosis in non-advanced stages of endometrial, ovarian and cervical cancers, stages in which the cancer is still treatable, combining the cytological screening of the routine Paptest with genetic screening of tumor DNA.
The development of kits that exploit the new NGS technologies fits well into the programmatic research objectives at regional, national and European level.
Description: Epithelial ovarian cancer (OC) is the leading cause of gynecologic cancer-related deaths in women, primarily because most patients present with advanced-stage disease. Moreover, in the last 20 years, the incidence rate of another gynecologic cancer, endometrial cancer (EC), has increased by 125% worldwide and despite improved diagnosis and treatment methods, up to 30% of EC patients are primarily diagnosed with stage III or IV EC and have poor outcomes. Cervical cancer, on the other hand, is much less frequent in developed countries thanks to the wide availability and effectiveness of screening with the Pap test (Papanicolau test) patients allowing for early diagnosis and surgical therapy. Unlike cervical cancer, for OC and EC there are no primary (vaccination) or secondary (population screening) prevention tools that allow for an early diagnosis and timely therapeutic intervention. Also, the identification of endometrial and ovarian cancer cells through microscopy examination of the specimen often fails to discriminate such cells from benign conditions or from cervical tumors.
Recently, it has been shown that malignant cells exfoliate from the ovaries and may be detected in Pap specimens, routinely collected through cervical cancer screening. By analyzing the cells shed from the cervix, the health state of other female reproductive organs, such as the ovaries, fallopian tubes and endometrium can be also evaluated. Endocervical DNA or intrauterine DNA can be obtained through vaginal tampons, intrauterine lavage, Pap smear, and Tao Brush to determine the presence of malignant tumor cells in the reproductive tract. Circulating tumor DNA is a type of cell-free DNA that accounts for a small part of circulating cell-free DNA. It is usually released from tumor tissues in vivo and harbors tumor-specific DNA mutations, which can be detected using massive parallel sequencing (NGS).
In this project, we will develop NGS-based tumor DNA screening tests on cervical specimens, with the potential to increase the chances of early detection of endometrial and ovarian cancers in asymptomatic women. The purpose of the new test is to facilitate the diagnosis in non-advanced stages of endometrial, ovarian and cervical cancers, stages in which the cancer is still treatable, combining the cytological screening of the routine Paptest with genetic screening of tumor DNA.
The development of kits that exploit the new NGS technologies fits well into the programmatic research objectives at regional, national and European level.
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ENTI TERZI - non associata a curriculum
- Tematica generica del dottorato
Ente finanziatore: IIT - Istituto Italiano di tecnologia
Competenze richieste: nessuna competenza specifica richiesta
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Il candidato sceglierà una o più tematiche in fase di presentazione della candidatura on line
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