Pelayo and zebrafish helping in rare diseases research

The multidisciplinary team composed by two different groups from the Faculty of Veterinary in Lugo (University of Santiago de Compostela): ZebraBioRes Group leaded by Laura Sánchez (on the right) and GAPAVET leaded by Maribel Quiroga (on the left).
The multidisciplinary team composed by two different groups from the Faculty of Veterinary in Lugo (University of Santiago de Compostela): ZebraBioRes Group leaded by Laura Sánchez (on the right) and GAPAVET leaded by Maribel Quiroga (on the left).

Congenital Disorders of Glycosylation (CDG) are a family of serious rare diseases, with a high complexity due to the variety of affected tissues and organs. They generally involve the central nervous system, the musculoskeletal, immune, digestive and endocrine systems, and coagulation. More than 150 different diseases are known within the CDG syndrome, which can show a variety of phenotypes (set of observable features in an organism). Approximately 170 patients have been registered in Spain, but most probably the real figure is much higher. For rare diseases, each patient is unique and requires a personalized treatment.

One “ultra-rare” variant, from which only 18 cases are described world-wide, is associated to a recessive mutation on gen RFT1. The majority of patients with this mutation demise prematurely or carry severe sympthoms such as psycomotor problems, epilepsy, hearing loss and digestive disorders.

One of the major constraints in the pursuit of the genes responsible for these rare diseases is the functional check, meaning the confirmation that certain changes lead to a certain disease. In the meanwhile, animal models are an useful tool for determining if one variant affects some process or functions related to a disease. Models are also an excellent tool for investigating the mechanism that triggers the disease, and for exploring possible treatments.

Zebrafish (Danio rerio) has proven to be essential for biomedical investigation as a model organism since, despite seemingly being too phylogenetically different from humans, there is a substantial homology with the human genome. Up to 85% of the genes that can induce diseases in humans are preserved in the zebrafish. Also, developing zebrafish models for studying genetic diseases is relatively easy. When the mutation associated to a certain disease is identified, it is possible to replicate it in the zebrafish, observe the associated symptoms, and determine the affected organs and systems through microscopic and molecular studies.

What is our goal?

Provided this, the main goal of our project is to develop, through CRISPR-Cas9 genetical edition technology, a zebrafish model useful for the study of “ultra-rare” diseases with extremely limited number of patients, for which the capability of a mutation to induce a disease needs confirmation. For such, a CDG subtype associated to a mutation in the RFT1 gene. From this point, a model will be available for studying the potential triggering factors, histologic, metabolic or physiological changes, and for testing specific treatments.

Only one patient with this mutation is known in Spain: Pelayo, a small two-year old superheroe who fights for carrying on and hopes for a small genetically modified fish to bring light to this disease and contribute to the pursuit of a treatment for affected children. This is not science-fiction! Several rare diseases have found a cure through similar strategies.

Who will benefit from our project?

This working methodology will be applicable to studying other CDG variants and other rare diseases. Research in this field will contribute to shed light on the fundamental mechanisms of glycosilation, which can also widely help to progress in the understanding of other common pathologies such as autoimmune diseases or cancer, among others.

Pelayo would also benefit, as the only known patient with this “ultra-rare” variant in Spainfighting for carry on at 2 years old, and other kids with the same disease.

Link to the project:

https://www.precipita.es/proyectos/Pelayo-y-el-pez-cebra-ayudan-en-la-investigacion-de-las-enfermedades-raras--/en

Read more

ZebraBioRes in involved in brain tumor project in collaboration with the hospital

Professor Laura Sánchez, Leader of ZebraBioRes group
Professor Laura Sánchez, Leader of ZebraBioRes group

ZebraBioRes is involved in a translational project involving researchers from the CiMUS (Santiago de Compostela) and the HULA (Lugo's Hospital) in order to find therapies to treat glioblastoma, working with patient samples and performing xenograft in zebrafish to get insight in the mechanisms that are underlying this type or rare brain tumor.

Link to the interview (in Spanish):

http://www.youtube.com/watch?v=ItDpGLyuO5E

Read more

Zebrabiores helps to get a deep understanding of pancreatic cancer using zebrafish model

Pablo Cabezas, Laura Sánchez Piñón and Juan Rubiolo, researchers of ZebraBioRes group. Foto: Álvaro Jesús Arana
Pablo Cabezas, Laura Sánchez Piñón and Juan Rubiolo, researchers of ZebraBioRes group. Foto: Álvaro Jesús Arana

Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), its nowadays one of the pancreatic tumors with the worst prognostic. It represents the fourth cause of death due to cancer, with a survival rate of 7-9% within the next 5 years since the diagnostic.

One of the factors that could explain this high mortality rate in this type of cancer and the inneficiency of the therapies applied to treat it, according to the researchers, would be one specific type of cancer cells known as cancer stem cells (CSC's). These cells are plastic and they have carcinogenic properties, apart from being chemoresistant and metastatic.

Zebrabiores group from the Veterinary Faculty (USC, Lugo) has participated providing the zebrafish as an in vivo model during the last 3 years in the research published in Nature Communications addressing the study of this type of cells in collaboration with the main group of the paper leaded by Dr. Bruno Sainz Anding (Instituto de Investigaciones Biomédicas "Alberto Sols" CSIC-UAM, Department of Cancer Biology) - https://sainzlab.com/

Read more

Our PhD Student Pablo Cabezas gave a talk in I3S research center in Oporto

Jose Bessa and Pablo Cabezas at the beginning of the talk in i3s auditorium
Jose Bessa and Pablo Cabezas at the beginning of the talk in i3s auditorium

Our PhD Student Pablo Cabezas gave a talk in the i3s research center in Oporto by the invitation of Jose Bessa.

The title of the talk was "Zebrafish avatars: a new ‘tiny’ weapon against cancer?" being a summary of his PhD thesis in the last 4 years, presenting results related to the improve of the xenotransplantation technique, image analysis and proof of concept of the methodology developed in the previous stages.

We would like to thank Jose Bessa for the invitation at the i3s, the possibility of giving this talk and all the explanations and information about his group and warm welcome!

Read more

Our advanced technician Ana Quelle Regaldie have done a one month stay at i3s in Porto

Ciudad de Oporto
Ciudad de Oporto

Ana Quelle Regaldie did a one month stay in June in the group of Isabel Silveira: “Genetics of Cognitive dysfunction” of the “Instituto de Investigação e Inovação” (i3S) of the University of Porto.  There, she learned molecular techniques of genetic edition to apply in her studies developing new zebrafish models of human diseases.

Read more

Our PhD Students Álvaro Arana and Carlos Coppel have done a brief stay at i3S in Porto

Instituto de Investigação e Inovação of the University of Porto (i3S)
Instituto de Investigação e Inovação of the University of Porto (i3S)

A month ago, PhD students Álvaro Arana and Carlos Coppel made a brief two-week stay in the José Bessa group, Vertebrate Development and Regeneration, of the Instituto de Investigação e Inovação of the University of Porto (i3S). There, they learned new molecular techniques to carry out their investigations and returned full of new ideas.

Many thanks to Jose Bessa and his team, we hope to meet again soon!

Read more

Zebrabiores group attended at the 2nd International FishMed Conference on Zebrafish Research

Poster presented in the congress
Poster presented in the congress

Zebrabiores group attended at the 10th Annual NGS & Clinical Diagnostics Congress in Warsaw, Poland. In this congress, PhD student Carlos Coppel, PhD student Alvaro Arana, PhD student Alba Pensado, PhD student Ana Quelle, PhD student Andrés Blanco presented a poster titled "Metaanalysis of different technical approaches in zebrafish models”.


ABSTRACT


Traditionally, mutant organisms have been widely used in various areas of research in order to test the function of genes involved in different biological processes. Random mutagenesis, based on mutagens such as ENU, has been the most used method to generate mutations in zebrafish. With the emergence of directed genome editing techniques: TALEN, Zinc Finger (ZFN) and especially CRISPR-Cas9, the generation of mutants has undergone an unprecedented revolution. On the other hand, reverse genetics techniques, being morpholinos the most used in zebrafish, have been questioned by the scientific community for its off-target effects and its low phenotypic correlation with mutants. Thus, in the present study a bibliographic review has been carried out, compiling a series of data from the different mutagenesis techniques. The aim is to cross these data and to learn about the efficacy of each technique and compare it with the efficacy derived from morpholinos.

Read more

Laura Sanchez interview in Gciencia: 'Zebrafish against the Costa da Morte ataxia'

Zebrafish adults exposed during the symposium of SCA36.
Zebrafish adults exposed during the symposium of SCA36.

NOP56 is the key. We know where is the mutation that share all the people affected by this disease, SCA36, or Dead Cost Ataxia. The symptoms of this disease are known (lose of balance and audition, problems to talk or walk) but we still do not know which is the mechanism for this mutation to cause all these symptoms.

In Lugo, Zebrabiores team, lead by Professor Laura Sanchez Piñón of the Genetics department, are studying the effect of the NOP56 mutation in zebrafish, a model organism that offers a lot of advantages for the experimentation.

Read more

Fishing for cures: The alLURE of using zebrafish to develop precision oncology therapies

Fishing for cures: The alLURE of using zebrafish to develop precision oncology therapies

REVIEW ARTICLE

By Matteo Astone, Erin N. Dankert, Sk. Kayum Alam and Luke H. Hoeppner

Zebrafish have proven to be a valuable model to study human cancer biology with the ultimate aim of developing new therapies. Danio rerio are amenable to in vivo imaging, high-throughput drug screening, mutagenesis, and transgenesis, and they share histological and genetic similarities with Homo sapiens. The significance of zebrafish in the field of precision oncology is rapidly emerging. Indeed, modeling cancer in zebrafish has already been used to identify tumor biomarkers, define therapeutic targets and provide an in vivo platform for drug discovery. New zebrafish studies are starting to pave the way to direct individualized clinical applications. Patient-derived cancer cell xenograft models have demonstrated the feasibility of using zebrafish as a real-time avatar of prognosis and drug response to identify the most ideal therapy for an individual patient. Genetic cancer modeling in zebrafish, now facilitated by rapidly evolving genome editing techniques, represents another innovative approach to recapitulate human oncogenesis and develop individualized treatments. Utilizing zebrafish to design customizable precision therapies will improve the clinical outcome of patients afflicted with cancer. 

npj Precision Oncology (2017)1:39 ; doi:10.1038/s41698-017-0043-9 

https://www.nature.com/articles/s41698-017-0043-9.pdf

 

 

Read more

Our Review "The Potential of Zebrafish as a Model Organism for Improving the Translation of Genetic Anticancer Nanomedicines" is now available online

Our Review "The Potential of Zebrafish as a Model Organism for Improving the Translation of Genetic Anticancer Nanomedicines" is now available online

This Review has been published in the special Issue Zebrafish: The Key for Cancer Treatment of the journal GENES. Titled The Potential of Zebrafish as a Model Organism for Improving the Translation of Genetic Anticancer Nanomedicines this publication is completely free online.

Authors: Carlha Gutiérrez-Lovera, Abi Vázquez-Ríos, Jorge Guerra-Varela, Laura Sánchez and María de la Fuente.

Abstract: In the last few decades, the field of nanomedicine applied to cancer has revolutionized cancer treatment: several nanoformulations have already reached the market and are routinely being used in the clinical practice. In the case of genetic nanomedicines, i.e., designed to deliver gene therapies to cancer cells for therapeutic purposes, advances have been less impressive. This is because of the many barriers that limit the access of the therapeutic nucleic acids to their target site, and the lack of models that would allow for an improvement in the understanding of how nanocarriers can be tailored to overcome them. Zebrafish has important advantages as a model species for the study of anticancer therapies, and have a lot to offer regarding the rational development of efficient delivery of genetic nanomedicines, and hence increasing the chances of their successful translation. This review aims to provide an overview of the recent advances in the development of genetic anticancer nanomedicines, and of the zebrafish models that stand as promising tools to shed light on their mechanisms of action and overall potential in oncology.

Available in http://www.mdpi.com/2073-4425/8/12/349

 

 

 

 

Read more

Laura Sánchez attended at the 10th Annual NGS & Clinical Diagnostics Congress

Laura Sánchez attended at the 10th Annual NGS & Clinical Diagnostics Congress

Laura Sánchez attended at the 10th Annual NGS & Clinical Diagnostics Congress in London, UK. In this congress our PhD student Alvaro Arana Díaz presented a poster titled "Generation of a zebrafish model of CHARGE syndrome by CRISPR-Cas9".

Abstract

CHARGE syndrome is a genetic disease that causes morphological abnormalities during development and is caused by haploinsufficiency due to mutations in the CHD7 gene. The zebrafish shares most of the genes with humans, including the chd7 gene. Thus we used CRISPR- Cas9 technology to provoke the appearance of mutations in this gene, and to generate a mutant line for the study of the disease. Recently, a relationship between this syndrome and the appearance of typical characteristics of senescence, such as a high expression of mediators of senescence p15 and p21, and a low cellular proliferation have been observed. Embryonic senescence is a process involved in the development of organisms, whereas CHARGE syndrome is a disease that causes morphological abnormalities during development. Given this relationship, we generated a mutant zebrafish CRISPR line for the chd7 gene, to perform a phenotypic characterization of the mutants, and to study the process of embryonic senescence in the mutants, evaluating the expression of genes related to senescence: p15 and p21 ; in addition to the chd7 gene, and perform SA-β-Gal staining to observe senescence in embryonic tissues. Our mutant embryos have different patterns in the SA-β-Gal activity and different levels of expression of the mediators of embryonic senescence, with respect to the WT embryos, which become noticeable from 120 hpf.

 

https://www.nextgenerationsequencing-congress.com/

 

 

Read more

3rd prize in a science photography contest

"A luz do saber", the 3rd prize winning photo.
"A luz do saber", the 3rd prize winning photo.

María Jesús Varela Pulpeiro (worker in the University Information Office) won the 3rd prize in the science photography contest, A Ciencia en Imaxe, organized by the University of Santiago de Compostela. 

Chus came to visit our lab and our zebrafish facility and she took several photos around. One of them was awared with the 3rd prize of the USC science photography contest.

http://www.usc.es/gl/centros/fisica/cimiv.html

http://www.usc.es/export9/sites/webinstitucional/gl/centros/fisica/imaxes/premios_cimiv/4_3premio.jpg

https://chusvarela.wordpress.com/

Read more

    Pursuant to Law no. 34/2002 on the Information Society Services, we remind you that this site is using cookies for the improvement of our services.

    Accept More information