Previous techniques could visualize active areas of transcription, but not give precise information about their shape and size. We imaged nascent RNA spatial accumulations, which we termed RNA nanodomains. We characterized the RNA nanodomains and revealed how they interact with active RNA Polymerase II, the main component of the transcription machinery, and in turn, with small chromatin clutches, one of the smallest units of organization of the DNA fibers.
Castells-Garcia et al. December 2021 Nucleic Acids Research
We showed that transcriptionally generated supercoiling regulates loop formation. The girl’s blowing represents the force of transcriptionally generated supercoiling that promotes loop extrusion (bubbles forming) through cohesin (ring of stick). Bubbles depict different nuclear topologies. Excess of cohesin, supercoiling, and loops leads to chromatin blending (upper bubbles), while inhibition of transcription or topoisomerases brings decreased supercoiling and chromatin compaction (lower bubbles). Cover art from Laura Martin.
Look at paper at this link: https://authors.elsevier.com/a/1dS8d3vVUPGJuH
ECaBox “Eyes in a Care Box”: Regenerating human retina from resuscitated cadaveric eyes.
We will create a device, the EcaBox, to resuscitate eyes from the dead. In collaboration with a number of Partners working in Universitat de Barcelona (UB), Institute for Bioengineering of Catalonia (IBEC), King’s College London (KCL) in the UK, the Association for the Advancement of Tissue Engineering and Cell Based Technologies & Therapies (A4TEC) in Portugal, AFERETICA in Italy and the Bar-Ilan University (BIU) in Israel, we will develop artificial blood, artificial vitreous to kick-starting the activity of retinal neurons and restoring eye function. ECaBox will be a transparent, cubic box that mimics conditions in the living human eye, maintaining the eye’s temperature and pH levels while avoiding blood clots and removing metabolic waste and toxins.
The Master Regulator protein BAZ2B can reprogram human hematopoietic lineage-committed progenitors into a multipotent state.
Arumugam et al. Cell Reports 2020
We used reverse-engineered networks to elucidate the molecular mechanism of cell-fusion mediated reprogramming of B lymphocytes to hematopoietic stem cell-like state. BAZ2B was identified as a Master Regulator that can reprogram human lineage-committed progenitors to multipotent hematopoietic cells, thus enhancing their stemness and long-term engraftment.
The Chemokine Receptors Ccr5 and Cxcr6 Enhance Migration of Mesenchymal Stem Cells into the Degenerating Retina
Inadequate migration and integration of transplanted cells into the retina limit the efficacy of cell therapy approaches. We found that chemokines released from the degenerating retina can drive migration of transplanted stem cells over-expressing Ccr5 and Cxcr6 receptors, thereby resulting in rescue of retinal degeneration.
Pesaresi et al. Molecular Therapy 2020
The first sino-spain meeting was held at GDL, Guangzhou, China. Talks from CRG PIs and GDL PIs were focused in the fields of chromatin structure, stem cell and regenerative medicine. Interactions between the two institutes were fostered to start a common PhD program that will be organised across the 2 continents. Students will spend part of the time at GDL in China and part of the time at the CRG in Spain carrying out research projects based on collaborations between PIs of the institutions.
Chromatin organization and gene expression are interdependent. Previously, our group had showed that nucleosomes form groups, termed clutches, whose size correlates with cell state.
In this paper, Alvaro, together with Jason Otterstrom, carried out 2-color super-resolution microscopy to image core histones and DNA at nanoscale resolution.
They identified the “clutch DNA” as the DNA whose compaction is dependent on the clutch. Moreover, they studied how the epigenetic state of the clutch alters the radius of the clutch DNA.
These results provide novel insights into chromatin organization at the nanoscale level and show how the clutches affect DNA packaging.