Dr. Moreno-Herrero (Oviedo, Spain), graduated in Physics by the University of Oviedo in 1998. Intrigued by the physical mechanisms of proteins and their interactions with nucleic acids, Fernando moved to Madrid to undertake a D. Phil. in Biophysics using the Atomic Force Microscope under the supervision of Prof. A. M. Baró. During his D. Phil., Fernando enjoyed three research internships for a total of eight months at the University of California at Berkeley under the supervision of Prof. C. Bustamante. Fernando´s PhD work (Cum laude, 1998-2003) was also awarded the Ph.D. Extraordinary Prize by the Universidad Autónoma de Madrid. On September 2003, Dr. Moreno-Herrero moved to The Netherlands to carry on postdoctoral research in single molecule biophysics at the Delft University of Technology under the supervision of Prof. C. Dekker. During his postdoctoral period with Prof. Dekker, Fernando focused his research on liquid AFM imaging and Magnetic Tweezers to study DNA-repair proteins interactions and the mechanical properties of nucleic acids. In December 2006, the PI started his own independent research line supported by the Spanish Ramón y Cajal program at the Fundació Privada Institut Catalá de Nanotecnologia (ICN) in Bellaterra, Barcelona. In september 2009, the PI secured a permanent position (Científico Titular) at the National Centre of Biotechnology, Madrid (CNB); a research institute of the Spanish National Research Council (CSIC), and since May 2017 he is Investigador Científico. Fernando leads the group of Single-Molecule Biophysics of DNA-repair Nanomachines at the CNB. Current research combines development of novel fast AFM technologies and Optical and Magnetic Tweezers machines with the aim to characterize and monitor the real-time dynamics of DNA repair processes at the single-molecule level.
Fernando has participated in 22 Research Projects, being the Principal Investigator in 13 of them, including a ERC Starting Grant 2007, a ERC Proof of Concept Grant 2014, and an ERC Consolidator Grant 2015. He has been also PI of three projects from MINECO. FMH has more than 92 publications, including 55 in ISI WoS Scientific jorunals, 28 conference proceedings and 3 book chapters. To date he has over 22 papers in journals with impact factor 9 or higher. His scientific papers accumulate over 2300 citations (WOS) and his H-index is 25. The average impact factor of his publications is around 8. Moreover, he has delivered 25 invited talks in national and international scientific conferences, including four plenary talks. He has been invited to present his work at Research Instutes or Scientific groups 21 times. Fernando has published his work in top multidisciplinary journals such as Nature, Nature Nanotechnology, Molecular Cell, The Proceedings of the National Academy of Sciences of USA, Physical Review Letters, The Journal of the American Chemical Society, Nano Letters, ACS nano, and Nucleic Acids Research among others. The impact of his research was recognized in 2012 by the Izasa-Werfen Prize of the Spanish Society for Biochemistry and Molecular Biology, in 2014 by the “Perez-Paya” Prize of the Spanish Biophysical Society, and more recently in 2015 by the “Miguel Catalán” Prize of the Autonomous Community of Madrid for researchers under 40.
Technical University at Delft
DNA repair complex Mre11
We investigated a protein nanomachine that we all need to repair inevitable damage to the DNA in our chromosomes, the Mre11 complex, an assembly of three proteins (Rad50, Mre11 and Nbs1). The Mre11 complex is essential for keeping our chromosomes together after DNA breaks, which occurs hundreds of times in all cells that are actively dividing. Un-repaired DNA breaks lead to cell death and incorrectly repaired breaks are a common cause of cancer. For instance, the Nbs1 component of this complex is defective in the genetic disease Nijmegen breakage syndrome, where patients have increased risk of developing cancer due to problems fixing chromosome breaks
TU Delft: Nynke Dekker and Cees Dekker
Erasmus MC Rotterdam: Martijn de Jager, Claire Wyman and Roland Kanaar
F. Moreno-Herrero et al. Nature 437 (7057), 440-443 (2005).
Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon DNA binding
AFM study of the interaction of Vaccinia Topoisomerase IB with DNA
We visualized and quantified the interaction between vaccinia topoisomerase IB (vTopIB) and DNA using the Atomic Force Microscopy. Type IB DNA topoisomerases cleave and rejoin one strand of the DNA duplex, allowing for the removal of supercoils generated during replication and transcription. Topoisomerases are essential for the survival of the cell and are a target for poisoning by anti-cancer drugs.
TU Delft: Laurent Holtzer, Daniel Koster, Cees Dekker and Nynke Dekker
Sloan-Kettering Institute: Stewart Shuman
F. Moreno-Herrero et al. Nucleic Acids Research 33(18), 5945-5953 (2005).
Atomic force microscopy shows that vaccinia topoisomerase IB generates filaments on DNA in a cooperative fashion
DNA bending on short length scales
The mechanics of DNA bending on intermediate length scales of 5–100 nm plays a key role in many cellular processes, and is also important in the fabrication of artificial DNA structures, but prior experimental studies of DNA mechanics have focused on longer length scales than these. We used high-resolution atomic force microscopy (AFM) on individual DNA molecules to obtain a direct measurement of the bending energy function appropriate for scales down to 5 nm.
TU Delft: Thijn van der Heijden, Cees Dekker
Whitehead Institute: Paul wiggins
Stanford University: Andrew Spakowitz
Cal Tech: Rob Phillips
Northwestern University: John Widom
University of Pennsylvania: Philip Nelson
P.A. Wiggins et al. Nature Nanotechnology 1, 137-141 (2006).
High flexibility of DNA on short length scales probed by atomic force microscopy
Unusual bending properties of hyperperiodic DNA
Several bioinformatics studies have identified an unexpected but remarkably prevalent 10 bp periodicity of AA/TT dinucleotides (hyperperiodicity) in certain regions of the Caenorhabditis elegans genome. Although the relevant C.elegans DNA segments share certain sequence characteristics with bent DNAs from other sources (e.g. trypanosome mitochondria), the nematode sequences exhibit a much more extensive and defined hyperperiodicity. Given the presence of hyperperiodic structures in a number of critical C.elegans genes, the physical characteristics of hyperperiodic DNA are of considerable interest. We investigated several hyperperiodic DNA segments from C.elegans using highresolution atomic force microscopy (AFM).
NOTE: This work was done in collaboration with Prof. Andrew Fire, who was awarded with the 2006 Nobel prize in Medicine.
TU Delft: Ralf Seidel and Nynke Dekker
Stanford University: Andrew Fire, Steven Johnson
F. Moreno-Herrero et al. Nucleic Acids Research 34(10), 3057-3066 (2006).
Structural analysis of hyperperiodic DNA from Caenorhabditis elegans
The persistence length of dsRNA
Over the past few years, it has become increasingly apparent that double-stranded RNA (dsRNA) plays a far greater role in the life cycle of a cell than previously expected. Numerous proteins, including helicases, polymerases, and nucleases interact specifically with the double helix of dsRNA. To understand the detailed nature of these dsRNA-protein interactions, the (bio)chemical, electrostatic, and mechanical properties of dsRNA need to be fully characterized. We measured the persistence length of dsRNA using two different single-molecule techniques: magnetic tweezers and atomic force microscopy.
TU Delft: Thijn van der Heijden, Jeroen Abels, Cees Dekker and Nynke Dekker
J.A. Abels et al. Biophysical Journal 88(4), 2737-2744 (2005).
Single molecule measurements of the persistence length of double-stranded RNA
Universidad Autónoma de Madrid
Non-intrusive AFM imaging methods in buffer
One of the main advantages of the AFM is the ability for imaging in buffers soft materials like biological samples. Despite this, imaging biomolecules in buffer is not simple and care must be taken in sample preparation and imaging conditions. One must adsorb molecules in such a way that the interaction with the supporting surface is weak enough to allow biomolecular interactions but also strong enough to be able to image them. We studied in detail different techniques for AFM imaging in buffer like Tapping, Jumping and Contact modes and evaluate the different sources of damage on soft biological materials
UAM: Pedro J. de Pablo, Jaime Colchero, Julio Gomez, Arturo M. Baro;
NANOTEC: Rafael Fernandez
F. Moreno-Herrero et al. Physical Review E 69, 031915 (2004).
Jumping Mode Scanning Force Microscopy: a tool for precise force control and high-resolution imaging in liquids
F. Moreno-Herrero et al. Ultramicroscopy 96, 167-174 (2003).
DNA height in Scanning Force Microscopy
F. Moreno-Herrero et al. Applied Surface Science 210, 22-26, (2003).
Jumping Mode Scanning Force Microscopy: a suitable technique for imaging DNA in liquids
F. Moreno-Herrero et al. Applied Physics Letters 81, 2620 (2002).
Scanning Force Microscopy Jumping and Tapping modes in liquids
F. Moreno-Herrero et al. Surface Science 453, 152-158 (2000).
The role of shear forces in scanning force microscopy: a comparison between jumping mode and tapping mode
Electrical propeties of DNA
Molecular devices are the final horizon in the miniaturization of electronic technology. The electrical transport properties of molecules are expected to differ dramatically from those of macroscopic conductors, and finding ways to measure these properties at such a small scale is an important challenge of the emerging nanoscience. In particular, DNA is a well-known molecule that appears as a promising molecular-wire candidate. We studied two direct procedures to measure electrical currents through DNA molecules adsorbed on mica and found a lower limit for the resistivity is 10^6 Ohm x cm in agreement with first principle calculations.
UAM: Pedro J. de Pablo, Cristina Gómez, Jaime Colchero, Adriana Gil, Mar Alvarez, Julio Gómez, José M. Soler, Arturo M. Baró
ICMB: Pablo Ordejón
UNIOVI: Pilar Herrero
NANOTEC: Rafael Fernández, Ignacio Horcas
F. Moreno-Herrero et al. Nanotechnology 14 (2), 128-133, (2003).
Topographic characterization and electrostatic response of M-DNA studied by Atomic Force Microscopy
C.Gómez-Navarro*, F. Moreno-Herrero* et al. Proceedings of the National Academy of Sciences USA 99 (13), 8484-8487 (2002).
Contactless experiments on individual DNA molecules show no evidence for molecular wire behavior
*Shared first authorship
C.Gómez-Navarro et al. Nanotechnology 13, 1-4 (2002).
Scanning force microscopy three-dimensional modes applied to the study of the dielectric response of adsorbed DNA molecules
P.J.de Pablo et al. Physical Review. Letters 85 (23), 4992-4995 (2000).
Absence of dc-conductivity in lambda DNA
Structural characterization of the Paired Helical Filaments
Paired helical filaments (PHF) is an aberrant structure present in the brain of Alzheimer’s disease patients which has been correlated with their degree of dementia. Several groups have indicated that the microtubule associated protein tau is the major component of PHF. Knowledge of the three-dimensional structure of the proteins implicated in neurodegenerative disorders is essential for understanding why and how endogenous proteins may adopt a nonnative folding. We studied the structure of the PHFs using AFM in air and buffer. Then, we compared our experimental results with structural models. From this we conclude that the PHF structure is compatible with two coupled ribbons with an overall height of 20 nm and a width of 10 nm.
UAM: Jaime Colchero, Julio Gómez, Arturo M. Baró
CBM-UAM: José J. Lucas, Miguel Díaz, Felix Hernández, Esteban Montejo, Mar Pérez, Jesús Avila
Fac. Med. -UAM: Pilar Gómez, María A. Morán,
Hospital Prynceps d´Espanya: Isidro Ferrer
CNB-UAM: José M. Valpuesta
M. Diaz-Hernandez et al. Journal of Neoroscience 24(42), 9361-9371 (2004).
The stable component of Huntington’s disease inclusions consist of amyloid-like huntingtin filaments that can be purified and that are susceptible to revert in vivo
F. Moreno-Herrero et al. European Polymer Journal 40(5), 927-932 (2004).
Jumping mode atomic force microscopy obtains reproducible images of Alzheimer paired helical filaments in liquids
F. Moreno-Herrero et al. Biophysical Journal 86, 517-525 (2004).
Characterization by atomic force microscopy of Alzheimer paired helical filaments under physiological conditions
F. Moreno-Herrero et al. Journal of Alzheimer’s Disease 3, 443-451 (2001).
Characterization by atomic force microscopy of tau polymers assembled in Alzheimer´s disease
Regulation of gene expression is fundamental in biological systems. A systematic search for protein binding sites in gene promoters has been done in recent years. Biochemical techniques are easy and reliable when analysing protein interactions with short pieces of DNA, but are difficult and tedious when long pieces of DNA have to be analysed. We studied the possibilities of AFM for identification of regulatory sequences. We used different transcription factors involved in the phosphate metabolism and glucose repression signalling of the yeast Saccharomyces cerevisiae.
UAM: Jaime Colchero, Arturo M. Baró
UNIOVI: Tamara de la Cera, Romina S. Chaves, Pilar Herrero, Fernando Moreno
T.de la Cera et al. Journal of Molecular Biology 319, 703-714 (2002).
Mediator factor Med8p interacts with the hexokinase 2: Implication in the glucose signalling pathway of Saccharomyces cerevisiae
F. Moreno-Herrero et al. Biochemical and Biophysical Research Communications 280, 151-157 (2001).
Imaging and mapping protein-binding sites on DNA regulatory regions with atomic force microscopy
F. Moreno-Herrero et al. FEBS Letters 459, 427-432 (1999).
Analisis by atomic force microscopy of Med8 binding to cis-acting regulatory elements of the SUC2 and HXK2 genes of Saccharomyces cerevisiae