• Istituto di Biologia e Patologia Molecolari

IBPM Highlights

17/09/2021

POR FESR 2014-2020 Avviso Pubblico “Gruppi di Ricerca - 2020”  Progetti finanziati



APTASER - Sviluppo di inibitori ad acido nucleico della serina idrossimetiltrasferasi nel tumore al polmone


DWARF - La felce Pteris vittata: una strategia green per eliminare l’arsenico dalle acque potabili

INNOVA3DIMAGING - Metodologie innovative di 3D high content imaging per la validazione di nuove molecole antitumorali

NEWPAT - Analisi genetica del DNA fetale circolante nel sangue materno: sviluppo di un test di paternità non invasivo ad elevata specificità

ORGANOVA - Sviluppo di modelli organotipici e organ-on-chip di tumore ovarico per testare farmaci antitumorali


SMART-BREED - Tecnologie molecolari innovative per l’adattamento delle specie ortive al cambiamento climatico mediante breeding di precisione




27/07/2021

Coordination of biradial-to-radial symmetry and tissue polarity by HD-ZIP II proteins

The female reproductive organ, the gynoecium, of the model plant Arabidopsis thaliana is, so far, the only known example studied at the molecular level of a developing structure that reprograms itself over time in order to achieve a transition from bilateral to radial symmetry.
In a study conducted at the IBPM-CNR in collaboration with the John Innes Center (UK) and CREA-GB (Rome), the role of the transcription factors HAT3 and ATHB4 in the transition from bilateral to radial symmetry during formation of the style, the apical part of the gynoecium, has been studied in the model plant Arabidopsis thaliana.
In previous studies, it had been shown that the change from bilateral to radial symmetry of the gynoecium occurs through various stages that can be described by a change in the distribution of the hormone auxin. In particular, in the apical part of the developing gynoecium, auxin allocation goes from a two foci distribution (bilateral symmetry) to one with 4 foci (biradial), and finally to a complete ring (radial). This process is cooperatively controlled by the transcription factors bHLH SPATULA (SPT), INDEHISCENT and HECATE1, 2 and 3. The related mutants, spatula and indehiscent are blocked at the bilateral two-foci stage, while the triple mutant hecate1, 2, 3 is blocked at the four foci stage. In the work just published in the journal Nature Communications, the role of HAT3 and ATHB4, two transcription factors known as direct targets of SPATULA, is described in the process that will lead to the formation of the radialized organ. In the work it is shown that the HAT3 and ATHB4 genes are also positively controlled by the HECATE genes in a cooperative way with SPATULA. Through genetic analysis, the use of inducible transcription factors and fluorescent markers, it was possible to establish that HAT3 and ATHB4 control the distribution of auxin and sensitivity to the hormone cytokinin. A negative feedback control of HAT3 and ATHB4 on the SPATULA gene was also observed. This regulation is most likely responsible for the correct balance of auxin and cytokinin hormone signaling over time and space, so as to allow the transition of symmetry and the formation of the correct radialized organ.
With this work, we want to remember our colleague Ida Ruberti, who sadly passed away during the final phase of this work, for her fundamental role in the conceptualization of the project and the in-depth discussions on the results.





07/07/2021

Aspettando la Notte Europea Dei Ricercatori Talenti per la Scienza - 7, 9 E 10 Luglio 2021



Documenti:

NET_TALENTI-PER-LA-SCIENZA.pdf
Mappa TALENTI-.pdf



06/07/2021

Biallelic mutations in RNF220 cause laminopathies featuring leukodystrophy, ataxia and deafness

We exploit Drosophila melanogaster to dissect the molecular mechanisms underlying neurologic and neurodegenerative disorders, and we are studying a novel form of leukodystrophy, linked to ataxia and sensorineural deafness.
Whole exome sequencing performed in several large consanguineous families, by our collaborators, allowed to identify two missense homozygous mutations that affect conserved residues of the ubiquitin E3 ligase RNF220, as causative events of a novel form of leukodystrophy. Mass spectrometry analysis identified lamin B1 as RNF220 binding partner. We demonstrated that RNF220 silencing in Drosophila specifically affects subcellular localization of fly lamin B1 orthologue, and promotes its aggregation. Further, RNF220 loss of function promotes significant neurodegenerative phenotypes in fly tissues, strongly supporting a functional connection between RNF220 and lamin B1.
Thus, we demonstrate that RNF220 is implicated in a novel form of leukodystrophy characterized by ataxia and sensorineural hearing loss, and show its role in the regulation of the nuclear lamina. Furthermore, we establish an in vivo fly disease model that could be exploited to design new therapeutic strategies.




03/06/2021

Prdm16-mediated H3K9 methylation controls fibro-adipogenic progenitors identity during skeletal muscle repair
Biferali et. al. (DOI: 10.1126/sciadv.abd9371)

In this work, we studied a mesenchymal stromal cell population (FIbro-Adipogenic Progenitros, FAPs) that plays a dual role in skeletal muscle homeostasis and regeneration. While they promote muscle regeneration by supporting paracrinally muscle stem cells. On the other hand having the potential to give rise to fibrotic and fat cells, they directly contribute to the degeneration of diseased muscles, such as those of patients suffering from Duchenne muscular dystrophy.

In this study we have identified a molecular mechanism of gene repression carried out by the Prdm16 / G9a / GLP proteins that is crucial in maintaining silent the ability of FAPs to promote the formation of muscle tissue.

In particular, this work shows that Prdm16 plays a fundamental role in blocking the regions of DNA encoding the muscle potential of FAPs at the nuclear periphery, recruiting the enzymes G9a and GLP to keep them silent. This discovery has an important translation and therapeutic potential. Indeed, the results of this work show that by inhibiting these proteins in mouse models of regeneration and dystrophy, it is possible to change the fate of these cells to consequently promote the regeneration of dystrophic muscles and, at the same time, slowing down their degeneration. In this work, we studied a mesenchymal stromal cell population (FIbro-Adipogenic Progenitros, FAPs) that plays a dual role in skeletal muscle homeostasis and regeneration. While they promote muscle regeneration by supporting paracrinally muscle stem cells. On the other hand having the potential to give rise to fibrotic and fat cells, they directly contribute to the degeneration of diseased muscles, such as those of patients suffering from Duchenne muscular dystrophy.
In this study we have identified a molecular mechanism of gene repression carried out by the Prdm16 / G9a / GLP proteins that is crucial in maintaining silent the ability of FAPs to promote the formation of muscle tissue.
In particular, this work shows that Prdm16 plays a fundamental role in blocking the regions of DNA encoding the muscle potential of FAPs at the nuclear periphery, recruiting the enzymes G9a and GLP to keep them silent. This discovery has an important translation and therapeutic potential. Indeed, the results of this work show that by inhibiting these proteins in mouse models of regeneration and dystrophy, it is possible to change the fate of these cells to consequently promote the regeneration of dystrophic muscles and, at the same time, slowing down their degeneration.

IBPM reference person: Chiara Mozzetta

Link: https://advances.sciencemag.org/content/7/23/eabd9371




04/03/2021

Cell Reports - Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK

DOI:https://doi.org/10.1016/j.celrep.2021.108800



Documents:
 Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK.pdf



01/02/2021

Among the winners of Start Cup Lazio 2020 there is the CNR team composed by Dr Patrizia Brunetti (IBPM-CNR), Dr Davide Marzi (IBPM-CNR) and Dr Giancarlo Daniele (EGATO-VT1),
with the project “Hydro Fern” that was awarded with the Special Mention "Social Innovation", the Special Lazio Region Award,
the 4th place and the access to the Premio Nazionale dell’Innovazione (PNI 2020).




Documents: 5_Green-Clean-Biotech_LAZIO7_Avvenire_24_01_2021_pag3.pdf

Links:

https://www.cnr.it/it/news/9768/una-green-revolution-del-cnr-tra-i-vincitori-della-startcup-lazio-2020
https://www.tg24.info/regione-start-cup-lazio-2020-i-vincitori-della-6a-edizione/
https://www.repubblica.it/economia/rapporti/impresa-italia/mercati/2020/10/27/news/ecco_i_vincitori_della_6a_edizione_di_start_cup_lazio_2020-272047189/



28/01/2021



In this study, we produced genome-wide sequences from 30 ancient individuals from western Russia, including 3 Stone Age hunter-gatherers (10,800 to 4250 BCE) and 26 farmers from the Bronze Age Corded Ware complex Fatyanovo Culture (2900 to 2050 BCE). The analyses of the ancient DNA data allow us to show that Eastern European hunter-gatherer ancestry was present in Russia already from 10,000 BCE. What is more, a change in the ancestry is observed with the arrival of farming in the area, with the Fatyanovo samples showing both Steppe and Early farmer ancestry, similarly to other Corded Ware groups. Finally, we were also able to assess the genotypes at 113 phenotype-informative markers, showing allele frequency changes in markers related to pigmentation and diet between hunter-gatherers and Fatyanovo farmers. In conclusion, our data seems to suggest that the Fatyanovo-associated people likely originate from a fast migration toward the northeast from a region near Ukraine, where Steppe and Early farmer ancestries coexisted from around 3000 BCE.

IBPM reference person: Eugenia D'Atanasio











15/12/2020


In this study we characterised the role of the Aurora-A kinase and its major regulator TPX2 in the control of mitotic spindle orientation in mammalian cells, a process which determines the position and fate of daughter cells. We highlighted a key role of TPX2 in the Aurora-A-mediated regulation of the orientation complex protein NuMA. We also describe opposite, microtubule-dependent, effects following increased Aurora-A or TPX2 levels in non-transformed cells, yielding-respectively- misoriented or “superaligned” spindles. Since high levels of Aurora-A and TPX2 are frequently observed in tumors, this study provides novel information to understand their pro-tumorigenic functions. It also opens the way to the investigation of the roles of the two proteins in other pathological contexts, particularly developmental or neurological disorders associated to defective cell division orientation.
Work was collaboratively carried out by groups at the Institute of Molecular Biology and Pathology (IBPM) and at the European Institute of Oncology (IEO). Research groups at Sapienza University and at the Max Planck Institute of Molecular Physiology (Dortmund, DE) participated to the project.

IBPM reference person: Giulia Guarguaglini




17/8/2020



 

Link at https://rdcu.be/b6jAd

www.immunophenotype.org

twitter: immunosurveillance@TheCrick


This study identified a “core” immune signature in the peripheral blood of COVID-19 patients. Blood T cells were typically characterized by co-existing lymphopenia and highly activated/proliferative phenotype, especially in severe patients. Some signature traits, including basophil and plasmacytoid dendritic cell depletion, and T cell-cycling, correlated with disease severity. Notably, a triad of molecules — IP-10, interleukin-10 and interleukin-6— anticipated disease worsening.

The study, called COVID-IP, was led by prof. Adrian Hayday (Francis Crick Institute, King’s College London, London, UK). A cohort of 63 hospitalized COVID-19 patients at Guy’s and St Thomas’ Hospitals (London, UK) was studied. Dr. Francesca Di Rosa (Institute of Molecular Biology and Pathology, CNR, Rome, Italy) was a member of the international team. She contributed to the novelty by introducing the innovative T cell assay for cell cycle analysis, that was used for the first time in COVID-19 patients in this study.


13/7/2020


This study highlights the impact of the noncoding side of the genome on neuronal differentiation. It reveals that the nuclear long noncoding RNA HOTAIRM1 contributes to shape human neurogenesis through a novel regulatory circuit, in which it controls the expression of the master regulator of neuronal fate, NEUROGENIN 2, and its downstream neurogenic cascade.

The identification in living cells of the protein FUS, crucially involved in Amyotrophic Lateral Sclerosis (ALS), as a direct interactor of HOTAIRM1 in motoneurons, together with the presence of a cytoplasmic isoform of HOTAIRM1 in motoneuron soma and neurites (yellow arrows), open the way for investigating a possible implication of this noncoding transcript in neurodegeneration.



This study derives from a collaboration between the Institute of Molecular Biology and Pathology (IBPM-CNR), the Department of Biology and Biotechnology (Sapienza University of Rome) and the Center for Life Nanoscience @Sapienza (IIT).

IBPM reference researchers: Pietro Laneve and Elisa Caffarelli



6/12/2019


IBPM at the Book Exhibition "Più libri più liberi": event on the DNA - WATCH THE VIDEO





Documents: PLPL_2019_PROGRAMMA_CNR.pdf



07/11/2019

In the school-work alternation project led by Maura Cardarelli and Patrizia Brunetti at IBPM, students of the Pascal High School train to use "green" technologies based on plant molecular biology to decontaminate soil from arsenic


Source: Rassegna Stampa CNR



08/10/2019

The 2019 Nobel prize to Physiology or Medicine for the discovery of the ability of cells to adapt to oxygen  levels

Comment by Alessandro Giuffrè
Source: https://www.cnr.it/rassegnastampa/19-10/191008/AJ1YUC.tif




23/07/2019



Astrobiology. ASI, the Italian Space Agency, supports the project "LIFE IN SPACE", including the IBPM Unit coordinated by Giovanna Costanzo. On PLATINUM https://platinum-online.com/, the new magazine distributed by Il Sole 24 ore


10/07/2019


Meeting with delegation from Ikiam University, Ecuador



Documents: Meeting with delegation from Ikiam University.pdf



Meet in Italy for Life Sciences 2019

Plant Cell


28/03/2019

Articolo di rassegna stampa

This study highlights a novel role of the metabolic enzyme serine hydroxymethyl transferase (SHMT), in supporting the high proliferative capacity of cancer cells.
 

Cancer cell

Cancer cells, especially in particularly aggressive tumors, e.g. lung carcinoma, have increased nutritional demands compared to normal cells. Understanding how tumor cells reprogram their metabolism to meet these demands, therefore, is key to understand the mechanisms that support the aberrantly high proliferation rate of cancer cells. The researchers have now identified a specific RNA that binds to and controls the function of the SHMT enzyme in the cytoplasm, while at the same time regulating the expression of a specific isoform found in mitochondria, the energy-producing centers of the cell.
 

Mito

 

The discovery paves the way for innovative therapies, aimed at designing nucleic acid molecules capable to act as metabolic "switches", so as to starve the tumor cells and hence block their proliferation.
 
This collaborative study is a joint effort between researchers from the Department of Biochemical Sciences "A. Rossi Fanelli" at the University La Sapienza and the Institute of Molecular Biology and Pathology (IBPM-CNR), in collaboration with the Department of Biology and Biotechnology (Sapienza), the Center for Genomic Regulation of Barcelona and the Catalan Institute of Oncology of Girona.

12/03/2019


13/02/2019
Alternanza Scuola-Lavoro: novanta ore per studiare antibiotici e SLA

Articolo di rassegna stampa


 


16/01/2019

During mitotic division genomic DNA is equally partitioned between the daughter cells, and several cellular machineries are reorganized to ensure faithful chromosome segregation. For example, cellular processes such as transcription and mRNA processing (“splicing”) are shut down during mitosis. The work by Pellacani et al. shows that two splicing factors, Sf3A2 e Prp31, are not inactive during mitosis but directly mediate proper kinetochore- microtubule interactions. These findings open the way to future research aimed at identifying new “moonlighting proteins” involved in both nuclear processes occurring during interphase and regulation of mitosis. An accurate understanding of mitosis at the molecular level is crucial to elucidate the mechanisms of tumorigenesis and develop new anti-cancer therapies.


DUCHENNE DISTROPHY: ENGINEERING A NEW ARTIFICIAL GENE FOR THERAPEUTIC PURPOSES

BBA
Documents: Press Review


PLANT MOCLECULAR BIOLOGY
"FRESH AS AN EXITRON": A NEW GROWTH REGULATORY MECHANISM DISCOVERED IN PLANTS
see Editorial Highlight in Plant Cell
 


Plant Cell
 
Documents: Plant Cell Editorial Highlight