Profile

Biography

Gonzalo Blanco is a lecturer in eukaryotic genetics in Biology since 2010. His PhD at the university of Seville (Spain) and first postdoctoral research at Sussex University focused on manipulating nitrogen fixation pathways in free-living bacteria. A highlight was the successful modification of Azotobacter vinelindii to excrete ammonium, patented work published in Molecular Microbiology and other journals. He switched fields in 1994 to study neuromuscular mouse models of disease with Prof Steve Brown at Imperial College and, later on, at the MRC Harwell. The association of two novel proteins, KY and PKD1L2, with muscle disease in the mouse are noteworthy findings from this period. His current research focuses on understanding the molecular basis of the muscle mechanosensor (s). 

Career

2010 -	Lecturer	Department of Biology, University of York
2003 - 2010	Programme Leader	MRC Mammalian Genetics Unit, Harwell
1998 - 2002	Investigator Scientist	MRC Mammalian Genetics Unit, Harwell
1996 - 1998	Post-doc	MRC Mouse Genome Centre, Harwell
1993 - 1995	Post-doc	St. Mary’s Hospital Medical School, Imperial College
1989 - 1992	Post-doc	University of Sussex
1989	PhD	University of Seville
1985	Degree	University of Seville

Research

Overview

Our objective is to elucidate mechanisms of neuromuscular disease and muscle hypertrophy. We aim to achieve this by exploiting mouse neuromuscular mutants to identify and study novel gene function in muscle. This is a sequential process involving generation of mouse mutants with a deficient neuromuscular system, description of the cellular pathology and in depth analysis of the underlying molecular players. The role of the KY protein in muscle function has been a continuous focus in the group since we discovered that the ky gene was responsible for a muscular dystrophy and a lack of normal hypertrophic response in the mouse. Muscle atrophy is a common denominator in all of our neuromuscular mutants, but this feature is particularly relevant in the ky mouse. We are currently addressing the hypothesis that novel players of the muscle hypertrophic process may be revealed by disentangling the KY protein complex.

Two references
1.    Jane Baker, Genna Riley, M. Rosario Romero, et al., and Gonzalo Blanco. (2010). Identification of a Z-band associated protein complex involving KY, FLNC and IGFN1. Experimental Cell Research, 316 (11): 1856-70.

2.    Francesca Mackenzie, Rosario Romero, Debbie Williams, et al., and Gonzalo Blanco. (2009). Upregulation of Pkd1l2 provokes a complex neuromuscular disease in mice. Human Molecular Genetics, 18: 3553-3566.

Discoveries

We discovered the genetic association of ky –a novel gene at the time- and Pkd1l2 -a homologue of the polycystic kidney disease gene- with distinctive neuromuscular diseases in the mouse. The corresponding proteins were unknown or functionally uncharacterized. The characterization of the KY protein lead to the discovery of a new muscle specific protein termed IGFN1. We have also shown that a recessive mutation in the most abundant skeletal muscle myosin in the mouse (MYHC IIb) causes a fulminant myofibrillar myopathy.

Current projects

• Molecular pathogenesis of ariel, a new conformational protein disease in the mouse caused by a mutation in Myosin IIB.
• Function in muscle development, adult skeletal muscle and heart of IGFN1, a new sarcomeric cytoskeletal protein.

Research group(s)

Technician
Sally Raines (50%)
Project title: Expression analysis of mutant and control myosin IIB in C2C12 myoblasts 

Available PhD research projects

Unraveling mechanotransduction in skeletal muscle (for 2012-13)

Elucidating the skeletal muscle mechanosensory complex is probably the single most important task in the field of muscle hypertrophy. In particular, unraveling the molecular sensors that detect mechanical loads and elicits signaling pathways to promote adaptive hypertrophy is crucial to design countermeasures to prevent loss of muscle mass. Indeed muscle atrophy is a common problem in bedridden conditions and aging and an important contributing factor to morbidity. We have recently described the KY protein as a novel member of the sarcomeric Z-disc (Baker et al., 2010, Exp Cell Res). The KY protein is required for adult muscle hypertrophy in the mouse and represents our best biochemical handle into the skeletal muscle mechanosensory hub (Beatham et al., 2004, Hum Mol Gen, Blanco et al., 2001, Hum Mol Gen). Muscles that lack the KY protein fail to respond to increasing mechanical loads, remaining atrophic and failing to withstand the mouse’s own body weight. In this project, proteomic analysis will first identify members of the KY complex. Candidate players will then be selected and tested for their ability to mediate a response to mechanical pressures by knocking-down their expression in vivo. This study will reveal pivotal players of the load induced hypertrophy pathway and will pave the way for further functional analysis of clinical relevance.

Publications

Selected publications

Gonzalo Blanco and Richard R Ribchester. Confocal microscopy of neuromuscular synapses in living mice. (2011). Current Protocols, in press.

Bernadett Kalmar, Gonzalo Blanco and Linda Greensmith. Determination of muscle fibre type in rodents. (2011). Current Protocols, in press.

Jane Baker, Genna Riley, M. Rosario Romero, Andrew R. Haynes, Helen Hilton, Michelle Simon, John Hancock, Vera M. Ripoll and *Gonzalo Blanco. (2010). Identification of a Z-band associated protein complex involving KY, FLNC and IGFN1. Experimental Cell Research, 316 (11):1856-70.

Francesca Mackenzie, Rosario Romero, Debbie Williams, Tom Gillingwater, Helen Hilton, Jim Dick, Joanna Riddoch-Contreras, Frances Wong, Lisa Ireson, Nicola Powles-Glover, Genna Riley, Peter Underhill, Tertius Hough, Ruth Arkell, Linda Greensmith, Richard Ribchester and Gonzalo Blanco. (2009). Upregulation of Pkd1l2 provokes a complex neuromuscular disease in mice. Human Molecular Genetics, 18: 3553-3566.

Frances Wong, Li Fan, Francesca Mackenzie, Michael Coleman, Gonzalo Blanco and Richard Ribchester. (2009). Axonal and neuromuscular synaptic phenotypes in Wld(S), SOD1(G93A) and ostes mutant mice identified by fiber-optic confocal microendoscopy. Mol Cell Neurosci. 2009 Aug 14.

Tucci V, Achilli F, Blanco G, Lad HV, Wells S, Godinho S, Nolan PM. (2007). Reaching and grasping phenotypes in the mouse (Mus musculus): A characterization of inbred strains and mutant lines. Neuroscience. 147(3), 573-582.

Beatham, J., Gehmlich, K., van der Ven, P., Sarparanta, J., Williams, D., Underhill, P., Geier, C., Fürst, D., Udd, B., *Blanco, G. (2006). Constitutive upregulations of titin based signalling proteins in KY deficient muscles suggest early titin involvement in the mechanism of pathogenesis Neuromuscular Disorders, 16:437-45.

Tucci, V., Blanco, G., Nolan, P.M. Behavioural and Neurological Phenotyping in the Mouse. In Standards of Mouse Model Phenotyping . Eds. Hrabé de Angelis, M., Chambon, P., Brown, S. (2006) Wiley-VCH, Weinheim, pp135-170.
9. Beatham J, Romero R, Townsend SK, Hacker T, van der Ven PF, *Blanco G. (2004). Filamin C interacts with the muscular dystrophy KY protein and is abnormally distributed in mouse KY deficient muscle fibres. Human Molecular Genetics 13: 2863-74.

Blanco, G., Pritchard, C., Underhill, P., Breeds, S., Greenfield, A., Brown, S.D.M. (2004) Molecular phenotyping of the mouse ky mutant reveals UCP1 upregulation at the neuromuscular junctions of dystrophic soleus muscle. Neuromuscular Disorders 14:217-228

Mburu, P., Mustapha, M., Varela, V., Weil, D., Aziz El-Amraoui, Holme, R., Rump, A.,  Hardisty, R., Blanchard, S.,  Coimbra,  Perfettini, I., Parkinson, N., Mallon, A., Rogers, M.,  Paige, A., Moir, L., Clay, J.,  Rosenthal, A.,  Liu, X., Blanco, G.,  Steel, K.,  Petit, C., Brown, S.D.M. (2003) Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and DFNB31 patients. Nature Genetics 34: 421-428.

Smith, L., Van Hateren, N., Willan,  J.,Romero, R., Blanco, G., Siggers, P., Walsh, J., Banerjee, R., Denny, P.,  Ponting, C., Greenfield, A. (2003) A candidate testis-determining gene, Maestro (Mro), encodes a novel HEAT repeat protein. Developmental Dynamics 227: 600-607.

Blanco G., Gary R. Coulton, Andrew Biggin, Christopher Grainge, Jill Moss, Michael Barrett, Anne Berquin, Georges Maréchal, Michael Skynner, Peter van Mier, Athena Nikitopoulou, Manfred Kraus, Chris P. Ponting, Roger M. Mason and Steve D. M. Brown. (2001) The murine kyphoscoliosis  (ky) mutant is a model for human idiopathic scoliosis and is caused by a mutation in a novel muscle specific protein. Human Molecular Genetics 10: 9-16.

Blanco G, (2000) Inherited muscle diseases: towards improvements of the mouse model catalogue. Current Genomics 1: 243-252.

Blanco G, Nikitopoulou A, Krauss M, Mason RM2, Coulton GR, Brown SD . (1998) A STS content physical and transcription map across the ky-kyphoscoliosis non-recombinant region. Genomics 54: 415-23.

Blanco G, Irving NG, Brown SD, Miller CC, McLoughlin DM. (1998) Mapping of the human and murine X11-like genes (APBA2 and apba2), the murine Fe65 gene (Apbb1), and the human Fe65-like gene (APBB2): genes encoding phosphotyrosine-binding domain proteins that interact with the Alzheimer's disease amyloid precursor protein. Mammalian Genome 9:473-475.

Blanco G, Brown SD. (1997) Genetic mapping of protein kinase C theta (Pkcq) to mouse chromosome 2. Mammalian Genome 8:70-71.

Joensuu T, Blanco G, Pakarinen L, Sistonen P, Kaariainen H, Brown S, Chapelle A, Sankila EM .(1996) Refined mapping of the Usher syndrome type III locus on chromosome 3, exclusion of candidate genes, and identification of the putative mouse homologous region. Genomics 38: 255-263.

Skynner, Mj., Gangadharan, U., Coulton, G.R., Mason, R.M., Nikitopolou, A., Brown, S.D.M. and G. Blanco. (1995) Genetic mapping of the mouse neuromuscular mutation kyphoscoliosis. Genomics 25: 207-213.

Blanco, G., Drummond, M., Kennedy C. and P. Woodley. (1993) Molecular analysis of the nifL gene of Azotobacter vinelandii. Molecular Microbiology 9: 869-879.

Ramos, F., Blanco, G., Gutiérrez, J.C., Luque, F., and M. Tortolero. (1993) Identification of an operon involved in the assimilatory nitrate-reducing system of Azotobacter vinelandii.  Molecular Microbiology 8: 1145-1153

Blanco, G., Hill, S., Kennedy, C. (1992) Excretion of ammonium by a NifL mutant of Azotobacter vinelandii fixing nitrogen. Applied and Environmental Microbiology 58: 1711-1718.

Contreras, C., Drummond, M. ,Bali, A., Blanco, G., Garcia, E., Bush, G., Kennedy, C. and Merrick, M. (1991) The product  of the nitrogen fixation regulatory gene nfrX of Azotobacter vinelandii is functionally and structurally homologous to the uridyltransferase encoded by glnD in enteric bacteria. Journal of Bacteriology 173: 7741-7749.

Blanco, G., Ramos, F., Medina, J.R., Tortolero, M. (1991) Conjugal retrotransfer of chromosomal markers in Azotobacter vinelandii. Current Microbiology 22: 241-249.

Blanco, G., Gutierrez, J.C., Ramos, F., Medina, J.R., Tortolero, M. (1991) R-primes from Azotobacter vinelandii. FEMS Microbiology Letters 80:213-216.

Blanco, G., Ramos, F., Medina, J.R., Tortolero, M. (1990) A chromosomal linkage map of Azotobacter vinelandii. Molecular and General Genetics. 224: 241-247.

External activities

Memberships

The Genetics Society
Member and local delegate

British Society for Cell Biology
Member

Open Journal of Genetics
Editorial board member