A5018736467- DNA and Nucleic Acid Chemistry
- DNA Repair Mechanisms
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Force Microscopy Techniques and Applications
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Mechanical and Optical Resonators
- Nanopore and Nanochannel Transport Studies
- Near-Field Optical Microscopy
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Neonatal Respiratory Health Research
- Molecular Junctions and Nanostructures
- Protein Structure and Dynamics
- Genetic Neurodegenerative Diseases
- Microfluidic and Bio-sensing Technologies
- Inhalation and Respiratory Drug Delivery
- Mycobacterium research and diagnosis
- Legume Nitrogen Fixing Symbiosis
- Advanced Electron Microscopy Techniques and Applications
Consejo Superior de Investigaciones Científicas
2016-2025
Centro Nacional de Biotecnología
2016-2025
The Francis Crick Institute
2022
Unidades Centrales Científico-Técnicas
2016-2019
Universidad Autónoma de Madrid
1999-2014
Delft University of Technology
2005-2007
Princeton University
2002
Universidad de Oviedo
1999
The electrical conductivity of biomaterials on a molecular scale is fundamental interest in the life sciences. We perform first principles electronic structure calculations, which clearly indicate that $\ensuremath{\lambda}$-DNA chains should present large resistance values. also two direct procedures to measure currents through DNA molecules adsorbed mica. lower limit for resistivity ${10}^{6}\phantom{\rule{0ex}{0ex}}\ensuremath{\Omega}\ifmmode \dot{}\else \.{}\fi{}\mathrm{cm}$, agreement...
Double-stranded (ds) RNA is the genetic material of a variety viruses and has been recently recognized as relevant molecule in cells for its regulatory role. Despite that elastic response dsDNA thoroughly characterized recent years single-molecule stretching experiments, an equivalent study with dsRNA still lacking. Here, we have engineered long molecules their individual characterization contrasting information same sequence. It known A-form unlike dsDNA, which exhibits B-form physiological...
We combine DNA origami structures with glass nanocapillaries to reversibly form hybrid nanopores. Trapping of the onto nanocapillary is proven by imaging fluorescently labeled and simultaneous ionic current measurements trapping events. then show two applications highlighting versatility these First, tuning pore size we can control folding dsDNA molecules ("physical control"). Second, that specific introduction binding sites in nanopore allows selective detection ssDNA as a function sequence...
The ParB protein forms DNA bridging interactions around parS to condense and earmark the bacterial chromosome for segregation. molecular mechanism underlying formation of these networks is unclear. We show here that while central binding domain essential anchoring at parS, this interaction not required condensation. Structural analysis C-terminal reveals a dimer with lysine-rich surface binds non-specifically condensation in vitro. Mutation either dimerisation or interface eliminates...
A fundamental requirement for a molecule to be considered molecular wire (MW) is the ability transport electrical charge with reasonably low resistance. We have carried out two experiments that measure first, transfer from an electrode molecule, and second, dielectric response of MW. The latter experiment requires no contacts either end molecule. From our we conclude adsorbed individual DNA molecules resistivity similar mica, glass, silicon oxide substrates. Therefore not conductor, it...
Significance The mechanical properties of nucleic acids regulate multiple biological processes ranging from complex chromosome packing to replication a plasmid. Single-molecule experiments have reported puzzling differences between the double-stranded DNA (dsDNA) and RNA (dsRNA) subjected force torque. This study investigates these using constant-force, all-atom, microsecond-long molecular dynamics. We provide physical mechanism that explains nonintuitive opposite twist-stretch response...
The segregation of many bacterial chromosomes is dependent on the interactions ParB proteins with centromere-like DNA sequences called parS that are located close to origin replication. In this work, we have investigated binding Bacillus subtilis in vitro using a variety biochemical and biophysical techniques. We observe tight specific homodimer sequence. Binding non-specific more complex displays apparent positive co-operativity associated formation larger, poorly defined, nucleoprotein...
Eukaryotic SMC complexes, cohesin, condensin, and Smc5/6, use ATP hydrolysis to power a plethora of functions requiring organization restructuring eukaryotic chromosomes in interphase during mitosis. The Smc5/6 mechanism action its activity on DNA are largely unknown. Here we purified the budding yeast holocomplex characterized core biochemical biophysical activities. Purified exhibits DNA-dependent SUMO E3 ligase activity. We show that binds topologically with affinity for supercoiled...
Faithful segregation of bacterial chromosomes relies on the ParABS partitioning system and SMC complex. In this work, we used single-molecule techniques to investigate role cytidine triphosphate (CTP) binding hydrolysis in critical interaction between centromere-like parS DNA sequences ParB CTPase. Using a combined optical tweezers confocal microscope, observe specific with directly. Binding around is enhanced by presence CTP or non-hydrolysable analogue CTPγS. However, proteins are also...
Significance Single-stranded DNA (ssDNA) is a key intermediate in many cellular transactions, including replication, repair, and recombination. Nascent ssDNA rapidly bound by the Replication Protein A (RPA) complex, forming nucleoprotein filament that both stabilizes mediates downstream processing events. Paradoxically, however, very high affinity of RPA for may block recruitment further factors. In this work, we show RPA–ssDNA filaments are specifically targeted human HELB helicase....
The capabilities of the atomic force microscope for imaging biomolecules under physiological conditions has been systematically investigated. Contact, dynamic, and jumping modes have applied to four different biological systems: DNA, purple membrane, Alzheimer paired helical filaments, bacteriophage \ensuremath{\varphi}29. These samples selected cover a wide variety systems in terms sizes substrate contact area, which make them very appropriate type comparative studies carried out present...
We report a method for simultaneous ionic current measurements of single molecules across up to 16 solid state nanopore channels. Each device, costing less than $20, contains glass nanopores made by laser assisted capillary pulling. demonstrate multichannel detection double stranded DNA and trapping origami nanostructures form hybrid nanopores.
Sequence-dependent DNA conformation and flexibility play a fundamental role in the specificity of DNA-protein interactions. Here we quantify crookedness: sequence-dependent deformation that consists periodic bends base pair centers chain. Using extensive $100\text{ }\text{ }\ensuremath{\mu}\mathrm{s}$-long, all-atom molecular dynamics simulations, found crookedness its associated are bijective, which unveils one-to-one relation between structure dynamics. This allowed us to build predictive...
Double-stranded (ds) RNA mediates the suppression of specific gene expression, it is genetic material a number viruses, and key activator innate immune response against viral infections. The ever increasing list roles played by dsRNA in cell its potential biotechnological applications over last decade has raised an interest for characterization mechanical properties structure, that includes approaches using Atomic Force Microscopy (AFM) other single-molecule techniques. Recent reports have...
Long noncoding RNAs (lncRNA) are emerging as key players in cancer parts of poorly understood molecular mechanisms. Here, we investigated lncRNAs that play a role hepatocellular carcinoma (HCC) and identified NIHCOLE, novel lncRNA induced HCC with oncogenic potential the ligation efficiency DNA double-stranded breaks (DSB). NIHCOLE expression was associated poor prognosis survival patients. Depletion from cells led to impaired proliferation increased apoptosis. deficiency accumulation damage...
Fluid jets are found in nature at all length scales, from microscopic to cosmological. Here we report on an electroosmotically driven jet a single glass nanopore about 75 nm radius with maximum flow rate ~15 pL/s. A novel anemometry technique allows us map out the vorticity and velocity fields that show excellent agreement classical Landau-Squire solution of Navier Stokes equations for point jet. We observe phenomenon call rectification: asymmetry respect voltage reversal. Such nanojet could...
Atomic force microscopy can potentially provide information on protein volumes, shapes, and interactions but is susceptible to variable tip-induced artifacts. In this study, we present an atomic approach that measure volumes of nonglobular polypeptides such as structural maintenance chromosomes (SMC) proteins, use it study the occur within between SMC complexes. Together with interest, coadsorb a DNA molecule fiducial marker account for artifacts affect both DNA, allowing normalization from...
Abstract A-tracts are A:T rich DNA sequences that exhibit unique structural and mechanical properties associated with several functions in vivo. The crystallographic structure of has been well characterized. However, the these is controversial their response to force remains unexplored. Here, we rationalize in-phase present Caenorhabditis elegans genome over a wide range external forces, using single-molecule experiments theoretical polymer models. Atomic Force Microscopy imaging shows...