Research and Education Reports Integrating Molecular Biology into the Veterinary Curriculum https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 Marion T. Ryan g Torres Sweeney ABSTRACT The modern discipline of molecular biology is gaining increasing relevance in the field of veterinary medicine. This trend must be reflected in the curriculum if veterinarians are to capitalize on opportunities arising from this field and direct its development toward their own goals as a profession. This review outlines current applications of molecular-based technologies that are relevant to the veterinary profession. In addition, the current techniques and technologies employed within the field of molecular biology are discussed. Difficulties associated with teaching a subject such as molecular biology within a veterinary curriculum can be alleviated by effectively integrating molecular topics throughout the curriculum, pitching the subject at an appropriate depth, and employing varied teaching methods throughout. Key words: molecular biology; education; veterinary; genomics; CAL INTRODUCTION Molecular biology is the modern branch of biology that explains biological factors, processes, and systems at a molecular level. It also encompasses biochemical and physical techniques used to investigate phenomena of molecular origin. The field of molecular biology integrates a number of areas of biology, particularly genetics, genomics, biochemistry, and cell biology (Figure 1), concerning itself with understanding the interactions between the various systems of a cell. The broad aim of scientists in this field include characterizing genomes, understanding influences on gene expression and regulation, gaining insights into the molecular structure and function of biologically important molecules, and identifying how such factors and molecules interact. In 1961, Astbury described molecular biology as follows: not so much a technique as an approach, an approach from the viewpoint of the so-called basic sciences with the leading idea of searching below the large-scale manifestations of classical biology for the corresponding molecular plan. It is concerned particularly with the forms of biological molecules and . . . is predominantly three-dimensional and structural—which does not mean, however, that it is merely a refinement Genomics Cell biology Molecular biology Genetics Biochemistry Figure 1: A schematic overview of the discipline of molecular biology. 658 of morphology—it must at the same time inquire into genesis and function.1 In parallel with the ever-widening body of knowledge and concepts within the field of molecular biology there is also an extensive, constantly expanding and evolving ‘‘toolbox’’ of techniques. Numerous technologies associated with the exploration of molecular biological phenomena have enabled researchers to explore veterinary-related research to new depths. In addition, molecular-biology techniques are increasingly being employed in veterinary diagnostics. The successful and meaningful integration of molecular biology into the veterinary curriculum is a difficult but necessary challenge for veterinary educators. APPLICATIONS OF MOLECULAR BIOLOGY IN VETERINARY MEDICINE The veterinary curriculum is constantly evolving and adapting to the changing needs of society. Leighton2 makes the point that if veterinary medicine is to serve society, there must be enough veterinarians to supply the demand for clinicians as well as ‘‘different’’ veterinarians who can work in an area other than clinical practice. Only then can veterinarians provide a unique perspective in areas such as bio-security, food safety, zoonotic diseases, ecology of health and disease, and management of the environment.2, 3 If veterinarians are to adopt new roles, they must acquire the required new skills and knowledge. The way molecular biology is being applied in veterinary practice and in wider areas of veterinary endeavor needs to be reflected in the curriculum. As Zemljit has written, The veterinarians of the future must be armed with new knowledge, which will be different from that needed today.4 Molecular biology is relevant to a wide range of core subjects within the veterinary curriculum and is applied in JVME 34(5) ß 2007 AAVMC Table 1: Important applications of molecular biology in veterinary medicine https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 Application Summary and Progress to Date Detection of breed-specific single-gene disorders and traits Numerous diseases and traits in domestic species have a single-gene etiology.6, 7 Once a singlegene disorder has been characterized, techniques such as PCR, RFLP, sequencing, and microsatellite analyses can then be employed to determine whether an animal carries the affected allele. Several of these single-gene traits/disorders have been identified in pedigree animals, including dogs,8 cats,9 horses,10 cattle,11 pigs,12 and sheep.13 Owners can then take this information into account when breeding. Various commercial companiesa–c offer services that can detect the presence of a variety of single-gene disorders, including canine leukocyte adhesion deficiency (CLAD), polycystic kidney disease, and severe combined immunodeficiency (SCID). Pathogen detection The routine use of molecular-based methods for human pathogen detection has been established for a number of pathogens in the clinical setting.14 A process of optimization, validation, and interpretation of results against clinical criteria is required when introducing a molecular test into the microbiology laboratory.15 The development of new molecular-based assays in the veterinary clinical setting has lagged behind human medicine, as companies have traditionally focused on developing assays and products tailored to human pathogen diagnostics. Increasingly, commercial companies are beginning to offer DNA-based pathogen detection as a service.d, e In addition to this some commercial companies, are beginning to invest in molecularbased products directed toward the veterinary diagnostic market. Artusf supplies optimized PCR kits that can be used for detection and quantification of pathogen load; these are available for Campylobacter, L. monocytogenes, M. paratuberculosis, and Salmonella. Qiageng is now promoting a range of products targeted at molecular diagnostics and research in veterinary medicine. Parentage testing Several companies offer parentage testing as a service.d, h DNA testing is available for a number of species, including horses,16 dogs,17 and cats.18 These DNA tests not only provide information relating to parentage but also serve as a unique genetic profile that can be used for identification purposes. Epidemiology Typing of pathogens is carried out using a range of molecular-based techniques, including plasmid analysis, pulse field gel electrophoresis, and multilocus allelic sequence-based typing.19 Epidemiologically related isolates share the same DNA profile, whereas unrelated isolates display patterns that are different from one another. These techniques allow investigators to trace the transmission of pathogens that have a negative effect on both production and animal welfare. Molecular-based typing also has a role in food safety, giving a better understanding of the mechanisms by which food-borne pathogens are transmitted. Monitoring antimicrobial-resistant strains such as Methicillin-resistant Staphylococcus aureus 20 and other zoonotic diseases is important from a public-health perspective. Using animal models to understand disease mechanisms and therapeutics in human medicine A wide range of animal models is used to explore the etiology of human diseases.21–23 Animal models are a useful means of exploring disease states, as the ethical restrictions are less stringent at a number of levels. Live-animal experiments, transgenic animals, breeding programs, and easy acquisition of tissue samples allow the completion of more comprehensive experiments than could ever be contemplated in human medical research. Animal cloning Of the 160 laboratories worldwide that carry out cloning experiments, 75% are working on livestock, including cattle, pigs, goats, and sheep.24 Cloning technology’s current low success rate, which is due to both technological and species-specific biological factors, 25 has hampered its economic feasibility.26 It has potential uses in the many areas, including basic research, generation of disease models, bioreactors, agricultural applications, and xenotransplantation. Xenotransplantation Xenotransplantation has attracted considerable interest in recent years and is continually moving closer to clinical application. This area of research is driven by the increasing demand for replacement organs and the short supply of suitable donors. The prime candidate animal in this field is the pig, which is most suitable in terms of breeding, rearing, cost, ethics, and anatomical compatibility to humans as well as because of its physiological and biochemical characteristics. The challenges in this area include graft rejection, acute inflammatory reactions, coagulation, physiological incompatibilities, and the danger of zoonosis transmission. Genetic engineering of donor animals has been seen as a way to overcome the challenges of acute rejection and coagulation.27 (Continued ) JVME 34(5) ß 2007 AAVMC 659 Table 1: Continued https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 Application Summary and Progress to Date Tailored pharmacology Pharmacogenetics explores variations in individuals’ responses to drug therapy based on their genotype (data from multiple genes). In veterinary medicine, a certain level of knowledge exists in this field, mainly relating to polymorphisms in single genes concerned with drug metabolism.28 Another example is the well-characterized adverse reaction to halothane anesthesia that occurs in pigs carrying a single-nucleotide polymorphism (SNP) in the ryanodine receptor.12 The understanding of pharmacogenetics in human medicine is considerably more advanced, as commercial interest is much greater. Current areas of interest in human medicine include cancer therapy,29 treatment of mood disorders,30 responses to cholesterol-lowering drugs,31 and variations in drug response between different ethnic groups.32 Quality-trait loci Quality-trait loci (QTL) are locations on the genome of genes or other genetic elements that contribute to the expression of a quantitative trait.33 Quantitative traits show different degrees of variation, depending on the trait, environmental factors, and the population in question. Quantitative traits include production traits such as meat quality,34 wool quality,35 and milk production;36 performance traits such as athletic performance;37 and non-production traits such as body conformation.38 QTL relating to disease susceptibility, such as mastitis in cattle39 and nematode resistance in sheep,40 are also of importance. All these traits are multifactorial, and many can have low heritability, which has hindered any genetic gains resulting from conventional selection and breeding.41 Efforts are underway to integrate QTL and phenotype data with sequence and gene maps in a database form.42, i Comparative genomics The comparison of genomes from different species, or comparative genomics, is now becoming possible as the genomes of more and more species are uncovered. Comparative genomics will give a greater insight into evolution, gene function, conserved regions, and non-coding DNA43 and is being employed as part of the functional annotation process.44 disciplines such as pathology, microbiology, endocrinology, parasitology, immunology, animal husbandry, pharmacology, embryology, and epidemiology (see Table 1 6–44). The discipline of molecular biology has enriched our understanding of many of these subject areas by allowing investigation of the underlying molecular processes within them. In embryology, for example, molecular biology has enabled developments that were formerly only described anatomically to be explained in terms of molecular processes and regulating factors.5 Molecular-biology technologies have direct application to veterinary diagnostics, veterinary epidemiology, and veterinary-related research. CHALLENGES OF DEVELOPING UNDERSTANDING IN BASIC MOLECULAR BIOLOGY THEORY Molecular biology is a challenging subject in itself; the subject matter is complex, and the scope wide. In the veterinary context, the material delivered needs to be suitably detailed but not so extensive as to encourage surface learning strategies.45, 46 When studying molecular biology, the student must commit a large amount of material to memory, including definitions, terminology, names of biologically active compounds, and biochemical processes and pathways. Memorization can be used to master unfamiliar terminology, as a first step toward understanding.47 The student must possess a basic knowledge of genetics, cell biology, and biochemistry, as well as a new lexicon for discussing these subjects, before progressing to the techniques and, finally, the applications of molecular biology in veterinary medicine (Figure 2). Many areas of molecular biology can be considered ‘‘troublesome’’ to students (Table 2). Perkins48 defines 660 Basic subjects Cell biology Biochemistry Gene structure and function Principles of inheritance and genetic disease Techniques and Technologies (See Table 1) Applications of molecular biology in veterinary medicine Diagnostic testing for genetically based disease states and disease susceptibility Epidemiology of pathogens Facilitating selective breeding programs for resistance to disease, enhanced production traits Genetic changes in neoplastic diseases Veterinary research Parentage testing Pathogen identification and quantification Pharmacogenomics Figure 2: An overview of molecular biology as a discipline within the veterinary curriculum. troublesome knowledge as that which is conceptually difficult, counterintuitive, inert, or alien. Troublesome knowledge is believed to originate from the student’s inability to grasp more fundamental and unifying concepts, termed ‘‘threshold concepts’’: conceptual gateways that are transformative, irreversible, and integrative and lead to a previously inaccessible way of thinking about the subject.49 Interestingly, these threshold concepts, once mastered, tend to give the learner a more privileged view of JVME 34(5) ß 2007 AAVMC Table 2: Selected troublesome areas in molecular biology, the nature of the difficulty, and related areas of knowledge and understanding https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 Troublesome Area Nature of Difficulty Related Knowledge and Understanding Higher organisms are composed of specialized, heterogeneous populations of cells that communicate with each other. Students may ‘‘know’’ this, but a true appreciation of the concept requires an understanding of the areas listed in column 3.





Cell signaling Signal transduction Receptors Competence Cell differentiation Differential gene expression Different cell types within an organism have differential patterns of gene expression, despite possessing the same genome. Students may ‘‘know’’ this, but a true appreciation of this concept requires an understanding of some of the areas listed in column 3.







Transcription Translation Gene regulation Differentiation Real-time PCR 2D gel electrophoresis Microarrays Cell signaling Protein metabolism, synthesis, and secretion
An appreciation of this concept requires an understanding of the areas listed in column 3.
The area contains a number of pathways that have to be memorized.
Students confuse digested protein with proteins that are synthesized by a cell.






Amino acids Codons Ribosomal, transfer, and messenger RNA Protein metabolism Protein storage and secretion Properties of proteins Post-translational modification Hardy/Weinberg equilibrium Abstract






Alleles Phenotype/genotype Genetic fitness Epistatis Inbreeding depression Genetic drift Evolution Genetic linkage Abstract
Genetic markers
Co-inheritance of undesirable traits with selected traits in animals Mendelian principles of inheritance Abstract



Dominant/recessive alleles Penetrance Phenotype/genotype relationship Inheritance patterns of single-gene diseases and traits Multigenic inheritance Abstract



Additive effects of genes Heritability Quality-trait loci (QTL) Selection and breeding strategies Polymerase chain reaction (PCR) Dynamic



Chemical characteristics of DNA DNA replication and synthesis Specificity of gene amplification Applications of PCR DNA sequencing Dynamic
Chemical characteristics of DNA
DNA replication and synthesis
Applications of electrophoresis Mitosis
Complex chain of events
Often represented in an unrealistic way
Students confuse chromosome number with the consequences of DNA replication at metaphase.




Chemical characteristics of DNA DNA replication and synthesis Cell division for growth and replenishment Regulation of the cell cycle Neoplasia Meiosis
Complex chain of events
Confused with mitosis
A link may not be established between the process and the consequences (see column 3).



Random segregation of genes Aneuploidy Gametogenesis Genetic variation https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 the discipline. Threshold concepts have been identified in a number of disciplines (e.g., the ideas of entropy in physics and of pain in medicine).50 Taylor51 highlights the difficulty of characterizing true threshold concepts within the biological sciences; rather, the real threshold concept relates to the complex and idiosyncratic nature of biological sciences. Biological knowledge is troublesome because of the high degree of interrelatedness of biological systems, the large number of processes, the constant need to reevaluate learned material in the light of new material, and the numerous layers of abstraction at which material can be viewed. Learning in biology usually requires the development of a gradually increasing awareness and constant re-evaluation of the topics being studied. Truisms taught at early stages are re-examined as further layers of complexity within the topic require a new set of truths to be constructed.51 These points relate strongly to the field of molecular biology, which, infinitely complex, underpins so many biological disciplines and can be viewed at numerous levels of abstraction. Some aspects of molecular biology require students to apply alternative metaphors or cognitive paradigms when trying to understand the same topic from a different viewpoint. A key example of this phenomenon relates to the understanding of genes. At the highest level of abstraction, genes are best viewed as particles or units (e.g., Mendelian inheritance and Hardy/Weinberg equilibrium).52, 53 This conception of genes must change, however, when learning about transcription and translation: genes must be viewed as having unique properties of their own, composed of promoter regions, introns/exons, and codons. The student must also be capable of viewing genes as a molecular compound (DNA) if they are to understand its molecular structure and chemical properties and before they can grasp the concepts of technologies such as PCR, DNA sequencing, and gel electrophoresis. In addition, the real-world relevance of molecular biology and its discussion in the public domain may result in some students’ having misconceptions about the discipline that may not concur fully with the understanding educators wish to instill.54 Entwistle and Smith47 suggest that the target understanding of genetics courses should build on or challenge ‘‘intuitive genetics’’ (i.e., that which is understood from everyday experience and the media) so that scientific meaning extends students’ existing understanding and relates it to their everyday lives. Efforts are currently underway to validate a series of questionnaires, collectively called the Biology Concept Inventory (BCI), aimed at accurately assessing students’ comprehension of concepts in introductory genetics, cell biology, and molecular biology.54 CHALLENGES IN DEVELOPING UNDERSTANDING OF MOLECULAR BIOLOGY TECHNIQUES AND TECHNOLOGIES Over the last 15 years substantial technological developments have taken place, enabling the detailed exploration 662 of molecular and cellular processes within the cell. These new technologies have become increasingly accessible, cost effective, and accurate. Developments and innovations within the computer and engineering industries have increased in response to the increased demand for the instrumentation that supports molecular-biology methodologies; numerous tools and technologies are now available that investigate cellular processes at a molecular level (see Table 355–66). Many of the technologies employed are complex and are operated by experienced personnel who become specialists in that particular technology. Other techniques are technically less complex and can be completed by personnel with less experience. The challenge for educators will be to decide how these essential technologies should be presented to veterinary students in a way that allows them to envisage molecular tools and technologies as something real as well as allowing them to appreciate both the potential of the technology and relevant applications of such technologies in veterinary medicine. Many of the recently developed molecular technologies are conceptually and technically complex (see Table 3). Approaches to teaching molecular biology to veterinary students must ensure that the subject is integrated with other veterinary subjects and that focus on the details of complex techniques and technologies is kept to a minimum. With reference to medical education, Jamieson supports this point by stating that non clinical teaching staff must accept that medical students do not necessarily need to know the depth and detail required by science students. The emphasis should be on learning of underlying principles, paradigms and clinically relevant examples.67 In contrast, life-sciences degree students may require a more in-depth and hands-on approach to molecular biology technologies, as these are a key aspect of their vocational training. If veterinary students become too immersed in the complexity of techniques, they may miss their relevance. Many textbooks illustrate landmark experiments; students often do not distinguish between the conclusion and the methods used to reach the conclusion, instead learning the material in a disconnected manner.68 Technologies such as microarrays and sequencing are technically complex and expensive, have long preparation times, and are currently not established as routine veterinary diagnostic tools. They are, however, important components within the discipline of molecular biology and are widely used in different areas of research. It is important that veterinary students know of the existence of these technologies, understand the underlying principles behind them, and know how and when they can be applied. Learning about molecular-biological techniques in the veterinary context poses another subtle problem that may not be appreciated by lecturers familiar with the techniques. The small volumes, nano-scale concentrations, and manipulation of what are essentially large molecules can make the subject seem inconceivable to many students. While this may not necessarily affect students’ theoretical understanding, it can affect their appreciation of the technology as something tangible and relevant. JVME 34(5) ß 2007 AAVMC https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 JVME 34(5) ß 2007 AAVMC Table 3: Selected techniques employed in molecular biology Technique Purpose Clinical and Research Applications Complexity Form of Data Generated Polymerase chain reaction (PCR)55 Amplification of specific gene targets Used clinically and in research. This technique can be used to detect a specific DNA template or to provide starting materials for further DNA analysis. Low Image of an ethidium bromide–stained gel, visualized under UV light Restriction fragment length polymorphism analysis Cutting DNA at specific sequence locations using restriction enzymes Used routinely in research; also used clinically. Can be used for rapid detectiong of SNPs without DNA sequencing. Low Image of an ethidium bromide–stained gel, visualized under UV light Agarose gel electrophoresis Separation of DNA or RNA on the basis of size This is one of the few ways that DNA and RNA can be visualized and, so it is used in all areas of molecular biology. Low Image of an ethidium bromide–stained gel, visualized under UV light Real-time PCR56 Relative and absolute quantification of specific gene targets originating from RNA or DNA Applied in research as means of exploring functional genomics and clinically in the determination of viral load, pathogen detection, and therapy monitoring Low–Moderate Image of amplification plot Numerical data in the form of CT values Microsatelite analysis (GeneScanj) Determination of size of DNA fragment (accurate to 1 base pair difference) by high-resolution polyacrylamide gel electrophoresis Parentage testing determination Moderate Image of fluorescently tagged PCR product and co-migrating size marker Numerical data relating to size Pulse field gel electrophoresis57 Separation of large DNA fragments Bacterial typing Moderate Image of an ethidium bromide–stained gel, visualized under UV lightNumerical data Bioinformatics58 Broadly encompasses the use of computational methods in the analysis of biological data. The tools used to analyze different types of data range from relatively simple algorithms to more complex multivariate analysis techniques. Expression data are analyzed using multivariate statistical methods and have extended to mathematical modeling, neural networks, and genetic algorithms.59 Analysis of sequence data, genome data, macromolecular structure, and gene-expression data. Variable (depends on complexity of data and analysis) Sequence and numerical data Epidemiology Allele (Continued ) 663 664 Table 3: Continued Purpose Clinical and Research Applications Complexity Form of Data Generated Automated DNA sequencing60 Determination of DNA sequence Used for research purposes; it can also be employed in diagnostics (i.e., to detect specific mutations) High Image of chromatogram Sequence data Microarrays61 Detection of differentially expressed genes Generally only used in research at present, but clinical applications are being explored High Image of Array Numerical data Two-dimensional polyacrylamide gel electrophoresis62 Separation of proteins based on both iso-electric point and molecular weight Generally only used in research at present, but clinical applications are being explored High Image of gel Matrix-assisted laser desorption/ ionisation time-of-flight (MALDI TOF)63 Provides accurate analysis of the molecular weight and structure of bio-molecules SNP genotyping Microsatellite typing characterization High Spectral data Flow cytometry64 Separation and characterization of cells Has both clinical and research applications High Numerical data Typing of SNPs and scoring haplotypes Has both clinical and research applications High Sequence data Selective disruption of distinct mRNA transcripts Defines gene function in vivo by knocking out or reducing gene expression at the post-transcriptional level; has applications in reverse genetics and therapeutics High Phenotypic analysis of cell or organism function Pyrosequencing RNA interference66 JVME 34(5) ß 2007 AAVMC https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 Technique 65 Protein NCBI’s repertoire of databases reflects the increasing interest in domestic species. The availability of whole genome sequences for many different species is, and will continue to be, an important resource contributing to comparative mapping initiatives, informing human medicine, and improving animal health and production.71 GENETIC DATABASES AND BIO-INFORMATICS https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 Sequence information is now integrated with related information, including gene and protein structure, conserved domains, and publications relevant to that sequence.69 Bio-informatics databases such as PubMedk are now the main source of molecular-biological information for graduate students.70 The automation of sequencing means that sequence data are being generated at an exponential rate. As of April 2006, there were over 130 billion bases in GenBank and RefSeq.k Databases such as those curated by the National Centre for Biotechnology (NCBI) and the European Molecular Biology Laboratory (EMBL) provide platforms for placing sequencing and genome data in the public domain (see Table 4). Over the last decade the major sequencing projects (see Table 4) have focused primarily on the sequencing of human genomes and those of model organisms such as mouse, E. coli, Drosophila melanogaster, and zebra fish. Subsequent genome projects have followed in the footsteps of the Human Genome Project, employing the most successful strategies and operating on a fraction of the budget.71 Largescale sequencing projects are now extending their interest to a number of domestic species, including cattle,72 horses,73 pigs,74 cats,75 dogs,76 and sheep.77 The recent addition of Online Mendelian Inheritance in Animals (OMIA)k to the APPROACHES TO TEACHING It is reasonable to assume that veterinary educators will differ in their approach to basic science education depending on whether they themselves work predominantly in a clinical or in a basic science environment. With regard to medical education, basic scientists may emphasize conceptual coherence over clinical application and favor teaching the basic sciences in more depth;78 it is felt that basic scientists do not feel fully confident in deciding the level of knowledge medical—or, indeed, veterinary—students need at graduation and may not tailor their teaching to emphasize clinical relevance, as they may not appreciate it fully themselves.78 Clinicians who are involved exclusively in clinical practice may understandably feel unconnected with the basic sciences; hence, despite its relevance to their area, they will be less likely to discuss a subject such as molecular biology in great depth. The fact that molecular biology is a rapidly evolving and growing discipline will increasingly exacerbate this problem. Table 4: Selected sequence and mapping databases, genome centers, and bioinformatics institutes Online Resource Web Address Comments National Centre for Biotechnology Information (NCBI) <www.ncbi.nih.gov> Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, and develops software tools for analyzing genome data. European Molecular Biology Laboratory (EMBL) <www.embl.org> EMBL’s mission is to conduct basic research in molecular biology; to provide essential services to scientists in its member states; to provide high-level training to its staff, students, and visitors; to develop new instrumentation for biological research; and ensure technology transfer. These core functions are combined with significant outreach activities in the areas of science and society and training for science teachers. DNA Databank of Japan (DDBJ) <www.ddbj.nig.ac.jp> DDBJ has been functioning as the international nucleotide sequence database in collaboration with EBI/EMBL and NCBI/GenBank. The Wellcome Trust Sanger Institute (WTSI) <www.sanger.ac.uk> The Sanger Institute is a genome research institute primarily funded by the Wellcome Trust. Their purpose is to further the knowledge of genomes, particularly through large-scale sequencing and analysis. The Institute for Genomic Research (TIGR) (J. Craig Venter Institute) <www.tigr.org> The Institute for Genomic Research (TIGR) is a non-profit center dedicated to deciphering and analyzing genomes. European Bioinformatics Institute (EBI) <www.ebi.ac.uk> The EBI is a center for research and services in bioinformatics. The institute manages databases of biological data, including nucleic acid, protein sequences, and macromolecular structures. Ensembl <www.ensembl.org> Ensembl is a joint project between EMBL, the EBI, and the WTSI to develop a software system that produces and maintains automatic annotation on selected eukaryotic genomes. Expert Protein Analysis System (ExPASy) <www.expasy.ch> The ExPASy proteomics server from the Swiss Institute of Bioinformatics (SIB) is dedicated to molecular biology with an emphasis on data relevant to proteins. JVME 34(5) ß 2007 AAVMC 665 Problem-based learning (PBL)82, 83 is a student-focused approach that aims to encourage students to construct knowledge and uncover concepts while developing analytical and critical thinking skills through a process of inquiry and reflection. It can be used as a means of integrating molecular biology with clinical scenarios at all stages of the curriculum; this approach has the potential to give students a more applied view of molecular biology. PBL can also motivate students to explore the many online resources and genetic databases outlined above. Electives and intercalated degrees in a molecular or biomedical subject afford veterinary students the opportunity to explore a career in research or diagnostics. This is important if students wish to deepen their existing understanding of molecular biology. Many molecular-biology experiments take a number of days or weeks to complete. Electives allow students to appreciate the inconsistencies, quality-control issues, and troubleshooting that take place continually in research and veterinary practice, as well as gaining a deeper insight into molecular and research concepts. ALTERNATIVE REPRESENTATIONS OF MOLECULAR BIOLOGY INFORMATION In view of the conceptual challenges the discipline of molecular biology presents to students, a significant amount of literature advocates the use of alternative representations in teaching this subject.84–86 Molecular biology is a broad and interconnected subject, and many processes within it are dynamic. Students need to appreciate the interconnectedness of molecular biology as well as knowing all its parts. This process takes time and will be more difficult for those studying at undergraduate level, who have not yet formed a global picture in their minds. Providing students with visual overviews and concept maps87, 88 can help them visualize the interrelatedness of molecular biological topics; this is particularly useful for students that have a strongly Wholist89 or Global90 learning style (see Figure 3). 666 16 14 12 Number of students In the broader context, teaching style is influenced by the lecturer’s perception of the students’ needs and prior knowledge, organizational support structures, timetabling constraints, and class sizes. Other influences include the lecturer’s own openness to varied teaching methods as well as his or her personal teaching and work responsibilities.79 Academics possessing a more holistic view of their subject adopt more student-focused approaches to teaching,80 including teaching methods such as tutorials, practicals, problem-based learning, and group discussions. Generally these teaching methods are considered superior to moreteaching focused approaches, such as lectures, but require greater effort and resources.81 Computer-aided learning (CAL) includes a wide range of tools, from online resources available in browser format to structured tutorials, simulations, animations, and multimedia presentations.91 CAL can offer students an alternative insight into areas that may otherwise be difficult to conceptualize.92 CAL can be particularly useful when applied to molecular biology education. Animations are available to illustrate dynamic topics such as PCR93 and automated sequencing (see Table 5), in addition to conceptually difficult areas such as Mendelian inheritance85 and population genetics.94 With reference to learning styles, learners with a strong preference for visual information as opposed to verbal information89, 90 may find CAL tools helpful (see Figure 4). 10 8 6 4 2 0 0 1 2 3 4 5 6 7 8 9 10 Score (Global) Figure 3: The distribution of scores from first-year veterinary students (N ¼ 75) for the global learning style on the global/sequential dimension, as determined by Felder’s Learning Styles questionnaire.l Students scoring above 5 show a preference for a global learning style. 14 12 Number of students https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 The involvement that many veterinary clinicians have in research containing a biomedical or molecular component may help to bridge the gap between clinical and basic sciences. This will not only increase awareness and knowledge of molecular biology among clinicians but also promote communication between teaching staff in clinical and basic sciences. Collaboration through research should give both parties a more holistic view of molecular biology as applied to veterinary medicine, which should have a positive impact on both teaching content and practice. 10 8 6 4 2 0 2 3 4 5 6 7 8 9 10 11 Score (Visual) Figure 4: The distribution of scores from first-year veterinary students (N ¼ 75) for the Visual learning style on the visual/verbal dimension, as determined by Felder’s Learning Styles questionnaire.l Students scoring above 5 show a preference for a visual learning style. JVME 34(5) ß 2007 AAVMC Table 5: A selection of freeware that can be used as educational tools to support education in molecular biology https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 Source Type of Application Web Address The Roche Genetics Education Program An interactive CD-ROM developed to promote basic awareness of genetics in the general public and to offer an interactive tool for learning basic principles of genetics <http://www.roche.com/home/science/ sci_gengen/sci_gengen_cdrom.htm> Howard Hughes Medical Institute (HHMI) Fully interactive biomedical laboratory simulations, animations, lectures, and video clips relating to different aspects of biomedical science, medicine, genetics, and evolution <http://www.hhmi.org/biointeractive/> Dolan DNA Learning Centre Animations for automated sequencing, PCR, DNA restriction, DNA transformation, DNA arrays <http://www.dnalc.org/ddnalc/resources/ animations.html> Davidson College Animation for microarrays <http://www.bio.davidson.edu/Courses/ genomics/chip/chip.html> Life Sciences Learning Centre Interactive animations for PCR, electrophoresis, genetic disorders, transcription/translation <http://lifesciences.envmed.rochester.edu/ animation.html> North Harris College Tutorials and multimedia animations in cell biology, genetics, molecular biology, and population genetics <http://science.nhmccd.edu/biol/ bio1.html#regulation> The World Wide Web is a useful educational recourse for molecular biology and genetics topics.95 Numerous freeware applications available online can be used to illustrate molecular biological techniques, including PCR, sequencing, and sub-cellular processes such as transcription and translation (see Table 5). The breadth of information that the Web gives students is extensive; this resource should be used with caution, as it may encourage unproductive browsing and students may encounter material that is beyond the scope of what is being taught at the time.96 PRACTICALS Practicals are widely employed in science education to illustrate theoretical information.97 Practicals in molecular biology can be difficult to conduct in any setting, as many of the techniques involved are too complex, time consuming, and expensive. Simpler techniques such as DNA extractions, PCR, and RFLP can be incorporated into a practical setting, but, like many molecular biological experiments, they may not be very visual and will have long preparation and incubation times.98 Many veterinary students may find the technical aspects of molecular biology uninteresting and irrelevant to their vocational training. Allowing students to interpret simplified outputs (see Table 3) from various technologies based on experiments relevant to veterinary practice is an inexpensive and relatively easy way of familiarizing them with the techniques and allowing them to appreciate their relevance. To date, little research has been carried out to confirm the educational merit of practicals; however, research undertaken on a cohort of veterinary medical students has illustrated that deep learning correlated with high ratings for practical classes as a teaching method.46 Further to this, two practicals—(1) DNA extraction and visualization and (2) scrapie genotyping—were evaluated98 in the context of students’ approaches to study.99 The scrapie-genotyping practical was rated higher and had a stronger association with deep learning than the JVME 34(5) ß 2007 AAVMC DNA-extraction practical. The format of the scrapie practical places less emphasis on technique and more on the application of molecular biology to clinical practice, and thus could prove much more useful for conducting a molecular biology–based practical class in the veterinary curriculum. VERTICAL INTEGRATION OF MOLECULAR BIOLOGY IN THE VETERINARY CURRICULUM Accreditation bodiesm–o have ensured that cell biology and molecular biology are included in the veterinary curriculum as a core subject at accredited institutions. The content and delivery of courses is at the discretion of the institution itself, and molecular biology is mainly taught as a discrete module or unit in the pre-clinical curriculum. Considering the relevance of molecular biology to so many areas of the veterinary curriculum, relatively little guidance is given on how to effectively incorporate this non-clinical subject into the veterinary curriculum. McCrorie100 comments that vertical integration in medical curricula is largely unidirectional. Clinical topics are integrated in the early years, when the basic sciences are principally taught, but efforts to reintroduce the basic sciences later in the curriculum are less actively driven as the course content acquires a more clinical slant. Coordinated vertical integration of molecular-biology topics is essential if veterinary students are to maximize their understanding of molecular biology and realize its applicability to clinical veterinary medicine. Nickerson101 describes ‘‘understanding’’ as an active process that connects factual information, relates newly acquired information, and weaves this knowledge into a cohesive whole. This process takes time. Reintroducing molecular biology at relevant points during the curriculum will not only reinforce the information already learned but also give veterinary students time to reflect on previously studied material while reevaluating it in the context of greater 667 clinical understanding. It is anticipated that this approach will deepen understanding, improve retention, and directly highlight the relevance of molecular biology to veterinarians. Gamulin, writing about medical education, supports this argument: The molecular medicine topics should be included into various subjects of undergraduate curricula and vertically integrated rather than treated as a separate subject in preclinical or clinical courses.102 https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 Koens et al. make an important point in favor of teaching basic sciences in the clinical context: Clinical context increases commitment to learn biomedical knowledge because it increases the willingness to invest more effort in the learning task.103 Achieving vertical integration of a non-clinical subject such as molecular biology demands a coordinated effort from teaching staff in relevant disciplines in all years. To determine how and at what level molecular biology learning materials should be incorporated at each stage of the curriculum requires coordination and communication between educators in the pre-clinical and clinical years. This goal can be achieved only through a conscious commitment. HOW MIGHT THE VETERINARIAN OF 2025 BE APPLYING MOLECULAR BIOLOGY? The veterinarians of 2025 could have a new range of molecular-based diagnostic tools at their disposal and, as a profession, may have new roles beyond the ones they currently play. However, concerns exist about the small numbers of veterinarians attracted to biomedical research,104, 105 as well as about the lack of non-clinical veterinary role models teaching in current veterinary program.3 The profession’s ability to capitalize fully on these new technologies will depend as much on how the profession broadens its own horizons as on the existence of the technologies in the wider arena. If veterinary diagnostics follows current trends in medical diagnostics, techniques such as PCR and real-time PCR will increasingly be employed as routine methods of pathogen detection,106, 107 SNP analysis,108 cancer diagnostics,109 and quantification of viral load.110 This technology will improve the speed of both diagnosis and treatment. Microarray technologies will not only help to characterize disease states but also provide information on the optimal course of treatment.111 The applications of molecular-based imaging techniques will also evolve in the clinical arena, giving the veterinarian a greater depth of clinical information beyond that currently available.112 One area that should significantly affect veterinarians will be the availability of data relating to the genome, proteome, and transcriptome of most species. By 2025, these data should be better annotated, and clearer phenotypic relationships established. Veterinarians may increasingly need to advise clients on genetic screening tests, which, in the future, could possibly involve the screening of multiple 668 genes on a chip-based format.113 The ongoing identification of QTLs and SNPs relating to animal health will become significant drivers for selective breeding in the future.38 Veterinarians will play a vital role in using this new information to advise breeders on animal welfare and health in production animals. It is reasonable to postulate that by 2025 the bio-informatics revolution may even have endowed veterinarians with tools that predict the final phenotypic outcome based on large quantities of genotype information, predicting the conformation and biological characteristics of a ‘‘virtual animal.’’ Breeding for health and welfare will be the ultimate step in preventive medicine. Veterinarians have important roles to play in comparative medicine and biomedical research.105 Veterinarians and those researching animal diseases will also play a vital role in informing human medicine, especially on issues relating to animal models, comparative genomics, and pharmacogenetics. Veterinarians’ current role in food safety and the traceability of zoonotic disease will be better facilitated by tools that permit the rapid identification and characterization of pathogens ‘‘in the field.’’ Rapid surveillance will be vital if antibiotic use is to be reduced.114 Transgenic technologies, which have the potential to confer new characteristics on existing species and even result in the creation of new species or breeds, may increase as a result of consumer demand. Veterinarians will play a role in advising on the health and welfare of these animals as well as treating them. Cloning technologies, if improved, could enable the conservation of rare,115 commercially valuable,24 or even extinct or endangered species,115 a scenario that will also generate unique clinical challenges for veterinarians. New areas of understanding (e.g., small interfering RNA,66 copy-number variation,116 and epigenetic variation117) are continually being uncovered in the field of molecular biology. This new understanding may also significantly affect diagnostics, treatment, and breeding strategies in some as yet unforeseen way. SUMMARY Molecular biology is increasingly affecting veterinary medicine, a trend that needs to be reflected on the veterinary curriculum. Effective incorporation of a non-clinical subject such as molecular biology onto the veterinary curriculum needs to be addressed in a way that maximizes understanding of the discipline without overloading students with unnecessary detail. The central concepts within molecular biology and its applications to veterinary medicine should be emphasized. Effective vertical integration will facilitate the teaching of molecular biology topics in the light of students’ understanding at the time, building on and reinforcing their existing knowledge and illustrating its applications in context. Effective communication among those contributing to molecular-biology education at different stages of the curriculum is essential if a global learning outcome is to be defined and implemented. Educators also need to be sympathetic to the learning challenges that molecular biology presents to veterinary students. In light of these particular challenges, a wide range of teaching methods and alternative representations JVME 34(5) ß 2007 AAVMC https://jvme.utpjournals.press/doi/pdf/10.3138/jvme.34.5.658 - Friday, July 22, 2022 8:45:52 AM - IP Address:18.206.222.211 should be employed to promote understanding of molecular biology. These learning challenges relate not only to the subject itself but to wider issues such as the necessary depth and breadth of material required by veterinary students. Haga95 clarifies this point further, stating that the goal of enhancing basic genetics education is to provide a foundation of knowledge that will allow learners to understand genetics concepts, applications, and ethical issues and become informed users of genetics technologies and their applications. <http://www.vgl.ucdavis.edu/service/parentage/ process.html>. i Bovine QTL Viewer, Texas A&M University <http://bovineqtl.tamu.edu>. j Applied BioSystems, Foster City, CA 94404 <http://www.appliedbiosystems.com>. k National Centre for Biotechnology Information (NCBI), Bethesda, MD 20894 <http://www.ncbi.nih.gov>. We believe that the core competencies that veterinary students should obtain in molecular biology include the following: l Felder R, Index of Learning Styles (ILS) <http://www2.ncsu.edu/unity/lockers/users/f/ felder/public/ILSpage.html>. Accessed 10/15/07. . an understanding of the background facts and concepts of molecular biology m American Veterinary Medical Association, Schaumburg, IL 60173-4360 <http://www.avma.org>. . knowledge of terminology and language specific to the subject n European Association of Establishments for Veterinary Education <http://www.eaeve.org>. . knowledge of the technology and techniques used to study and investigate molecular processes o Australasian Veterinary Boards Council <http://www.avbc.asn.au/>. . an understanding of the potential applications of molecular biology to veterinary medicine . an understanding of the wider implications of employing molecular-based technologies in veterinary medicine and to society The means by which these learning goals are achieved within any individual veterinary institution is still a matter of choice. 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Epigenetic reprogramming in mammals. Hum Mol Genet 14(Suppl 1):R47–R58, 2005. AUTHOR INFORMATION Marion T Ryan, MSc, D.Med.Sci., is a Senior Technical Officer in the Molecular Biology Facility, College of Life Sciences, School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Republic of Ireland. E-mail: marion.ryan@ucd.ie. She has published in a number of areas including distance education, computer-aided learning, learning approaches, veterinary embryology, and molecular genetics. Torres Sweeney, PhD, is a Senior Lecturer in Cell and Molecular Biology in the College of Life Sciences, School of Agriculture, Food Science and Veterinary Medicine and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Republic of Ireland. E-mail: torres.sweeney@ucd.ie. Her major research interests are: genetic polymorphisms in commercially important traits in bovine and sheep, gene expression profiling of meat-quality traits, and immunogenomics of disease resistance in livestock animals. 673