Animal models applied to human research

To know the methodology and technologies employed in the generation of animal models.
To understand the National and International legislation on the use of Laboratory Animals.
To know the techniques on Genetic Editing and Generation of mutant and transgenic lines.

1. The Zebra fish as a model for Biomedical Research.
2. Generation of models in rodents. From the phenotype to the gen: Inducible Mutations.
3. Genetically Modified Organisms (GMOs). Overexpression Transgenesis. Knock-out and knock-in mice.
4. New technologies of genetics editing: CRISPR
5. Models of human diseases: Neurodegenerative diseases, dystrophies, genetic diseases, infections and aging.

• THEORETICAL LESSONS
LESSON 1. The Zebra fish as a model for biomedical research.
Part 1. Introduction to Zebrafish: Overview, Life Cycle, Maintenance and Genome. Toxicity and biodistribution: compounds and cells.
Part 2. Genetic modification of Zebrafish in biomedicine.
LESSON 2. Use of zebrafish for modeling human diseases
Part 1. Modeling of cancer in Zebrafish
Part 2. Modeling of aging in Zebrafish
LESSON 3. Animal Models of Human Diseases I. Complex hereditary diseases. Murine models of cancer immunotherapy.
LESSON 4. Animal Models of Human Diseases II. Simple hereditary diseases.Murine models of Hypohidrotic Ectodermal Dysplasia.
LESSON 5. New technologies of Genetic Editing.
LESSON 6 (Seminars) Pathology of rodents. Immunology in Transplants. General techniques for handling Zebrafish embryos, sampling and phenotypic characterization.
LESSON 7 (Self-Directed learning of the student). Relevant Bibliography on Animal Research in the Galician Autonomous Community and at National and European level.

• PRACTICAL LESSONS
LESSON 1. Rat and Mouse necropsy and sampling. Embryo processing
LESSON 2. Generation and characterization of Zebrafish mutants using the CRISPR/Cas9 technique.

Basic Bibliography:
• Abate-Shen C., Politi K., Chodosh L., Olive K.P. (Eds). 2014. Mouse Models of Cancer: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
• Bravo Moral, A.M. (2019). Técnica de necropsia y toma de muestras en rata y ratón. Monografías do Ibader - Serie Pecuaria. Ibader. Universidade de Santiago de Compostela. Lugo. Acceso libre: http://www.ibader.gal/ficha/136/927/Tecnica-de-necropsia-y-toma-de-mues…
• Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M., Collins J.E., Humphray S., et al. 2013. The zebrafish reference genome sequence and its relationship to the human genome. Nature, 496: 498-503.
• Hwang W.Y., Fu Y., Reyon D., Maeder M.L., Tsai S.Q., Sander J.D., Peterson R.T., Yeh J.R., Joung J.K. 2013. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nature Biotechnology, 31: 227–229
• Melenchón Ramírez, F, Collins Rosado B, Bravo del Moral AM (2018). Manejo de animales de experimentación. Xunta de Galicia. Consellería do Medio Rural. Santiago de Compostela. Acceso libre https://libraria.xunta.gal/es/manejo-de-los-animales-de-experimentacion
• Zon L.I., Peterson R.T. 2005. In vivo drug discovery in the zebrafish. Nature Reviews Drug Discovery, 4: 35-44.
• Yang H., Wang H., Jaenisch R. 2014. Generating genetically modified mice using CRISPR/Cas-mediated genome engineering. Nature Protocols, 9: 1956–1968.


Supplementary Bibliography:
- Cook M.I. (edited by), The Anatomy of the Laboratory Mouse, Academic Press, London and New York, 1965.
- Dunn T.B., The Importance of Differences in Morphology in Inbred Strains, J. Nat. Cancer Inst., vol. 15, 573-85, 1954.
- Hedrich HJ & Bullock G. The Handbook of Experimental Animals. The Laboratory Mouse, Elsevier Academic Press, Amsterdam, 2004
- Maronpot R R. Pathology of the Mouse, Cache River Press, USA, 1999.
- McInnes E, Background Lesions in Laboratory Animals. A color atlas, Saunders Elsevier, UK, 2012
- McInnes E (editor). Pathology for Toxicologists. Principles and practices of Laboratory Animal Pathology For Study Personnel. John Wiley & Sons Ltd, Wiley Blacwell, UK, 2017
- Percy DH & Barthold SW. Pathology of Laboratory Rodents and Rabbits. Blackwell Publishing, UK, 3rd edition 2007.
- Rossant J & Tam PPL, Mouse Development. Patterning, Morphogenesis, and Organogenesis. Academic Press, San Diego, USA, 2002
- Rugh R. The Mouse. Its Reproduction and Development, Oxfor University Press, UK, 1990.
- Ward JM, Mahler JF, Maronpot RR, Sundberg JP, Frederickson RM, Pathology of Genetically Engineered Mice. Iowa State University Press, a Blackwell Publishing Company, USA, 2000.

Other learning resources:
• The Zebrafish Information Network
• https://zfin.org/
• Zebrafish Mutation Project
• http://www.sanger.ac.uk/resources/zebrafish/zmp/
• The Jackson Laboratory https://www.jax.org/
• Teaching resources from the American Association of Immunologists. https://www.aai.org/Education/Teaching-Resources
• Immunology animations
https://www.wpunj.edu/sec/vsec/science_courses/bio/BIOimmuANIM.html

Basic Competencies
CB7 – Students must know on how to apply the acquired knowledge as well as their capacity to solve problems in new situations and poorly known or multidiscipline contexts.
CB8 – Students must be able to integrate the knowledge and face the complexity of setting a critical judgement based on incomplete or limited information available, including reflexions on the social and ethical responsibilities derived from the application of their knowledge and judgements.
CB9 – Students must be able to communicate their conclusions and knowledge as well as the ultimate reasons sustaining them to a specialised or a general public in a clear unambiguous way.

General Competencies
CG01 – To acquire the capacity to organise and plan the study and research in a given area
CG02 – To integrate the knowledge and make decisions based on scientific and technical information.
CG03 – To transmit the results from their study and research activities to specialised, academic or general public.

Specific Competencies:
CE02 – To know the safe methodologies and techniques of modern Genetics and Genomics in order to apply them to a variety of production fields.
CE05 – To acquire knowledge and skills in the development of a scientific work in any Health Science or, at least in the following areas: Genetics, Physiology, Pathology, Legal and Forensic Medicine, Animal Production, Vegetable Production.

Soft/Transversal Competencies:
CT04 – Capacity to learn and integrate in multidiscipline working groups, to cooperate and show team spirit, even in an international framework.
CT07 – Capacity to elaborate, expose and discuss a scientific or technical document in an organised and comprehensive way

Theoretical and practical lessons would be synchronous online sessions, with mandatory presence and/or activities through content in the virtual classroom
Critical reading and analysis of documents supplied by the teacher synchronously online or by using of the virtual classroom.
Development and frontal exposition of academic work.
Personal frontal tutorials and/ or on-line tutorials.
Individual study of the student would not be face to face.

• Written exam: students must sit a written exam in order to demonstrate the acquisition of theoretical contents (it will account for 60% of the final mark)
• Assessment of Practicals: Students must sit an exam to demonstrate the acquisition of practical skills (it will account for 20% of the final mark)
• Continuous Assessment: Students attitude in the theoretical and practical sessions will be assessed together with his/her quality and clarity to expose self-directed work (it will account for 20% of the final mark). By the end of frontal lessons (theoretical or practical) some assessment by digital platform would be optional under the discretion of the teacher (for example Kahoot)

The in Classroom Workload: 24 hours
Lectures (expositive and interactive): 7 hours
Practical lessons (expositive and interactive): 7 hours
Other training activities, seminars, IT activities: 5 hours
Personal Tutorials: 3 hours
Exam: 2 hours
Self-Directed Learning and Individual Study of the Student: 51 hours

It is very convenient to have taken previously some basic knowledge on Genetics and Genomics in order to get the optimal academic progress.
It is convenient to have basic computer knowledge to navigate the Internet and word processors to handle documents (Microsoft Word, ..) and images (Microsoft PowerPoint).
Since some theoretical and practical content will be taught in English, and many research articles and books recommended in the bibliography are in English, we strongly recommend an acceptable level in this language.
To maximize the study of the subject we recommend the student:
- Regular attendance to lectures.
- Use of the materials provided by teachers as a study guide: outlines, notes, etc.
- Use of recommended general and special learning resources: textbooks, atlas, Web pages ...
- Regular use of the tutorials to solve questions and problems.
- Constant study throughout the semester.
- Pro-active participation and asking of questions during the frontal sessions

In the subject we regularly employ the virtual platform. Thus we strongly recommend the students to pay attention to the constant news published in the virtual subject.