{"id":8012,"date":"2023-02-08T17:30:08","date_gmt":"2023-02-08T17:30:08","guid":{"rendered":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/?p=8012"},"modified":"2023-03-05T10:17:51","modified_gmt":"2023-03-05T10:17:51","slug":"its-a-knockout","status":"publish","type":"post","link":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/2023\/02\/08\/its-a-knockout\/","title":{"rendered":"It&#8217;s a knockout!"},"content":{"rendered":"<div class=\"wp-block-image is-style-rounded\">\n<figure class=\"alignright size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.medsci.ox.ac.uk\/images\/folding-genome\/2m-dna-in-every-cell\/responsive_image?ratio=image&amp;scale=w760\" alt=\"\" width=\"144\" height=\"81\" \/><\/figure><\/div>\n\n<div class=\"wp-block-image is-style-rounded\">\n<figure class=\"alignright size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/images.fineartamerica.com\/images\/artworkimages\/mediumlarge\/2\/dna-family-erzebet-s.jpg\" alt=\"\" width=\"118\" height=\"83\" \/><\/figure><\/div>\n\n\n<p>The human genome is \u201cpacked\u201d in a particular molecule called DNA, which composes the core of our cells. This molecule is extremely big; if we could completely stretch it, it would be 2 metres long!&nbsp;<\/p>\n\n\n\n<p>This incredible molecule, DNA, is composed of 2 main regions: coding and non-coding regions. The non-coding region is significantly more abundant and composes 98% of the total of our genome, while the coding genome only the remaining 2%. However, the coding region is hugely important, as it makes proteins, the basic functional units responsible for the smooth running of our body.<\/p>\n\n\n<div class=\"wp-block-image is-style-rounded\">\n<figure class=\"aligncenter size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/cmsasset.ancestrycdn.com\/content\/dam\/ancestry\/magnolia-dam\/seo-dna-lp-images\/non-coding-dna.png\" alt=\"\" width=\"589\" height=\"219\" \/><\/figure><\/div>\n\n\n<h2 class=\"has-text-align-center wp-block-heading\"><strong>How do we identify and study the function of each coding region of DNA that makes a specific protein?<\/strong><\/h2>\n\n\n\n<p>The scientific method utilised is called \u201cknockout\u201d, which refers to the use of genetic engineering to inactivate or remove one or more specific genes from an organism. In order to explore the function of a particular gene and study the effect of its loss, scientists historically used genetic engineering to create knockout organisms to study the impact of removing a gene from an organism, allowing the discovery of a gene\u2019s functions.<\/p>\n\n\n\n<p>For instance, rather than study the gene directly, it is easier for scientists to study the final product of a gene, its protein. Moreover, since the cell is composed of thousands of different genes that encode a massive range of proteins, how can we identify the function of THAT specific gene without concretely isolating it from the such chaotic \u201ccrowd\u201d?&nbsp;<\/p>\n\n\n\n<p>The most commonly used animal model for knockouts is mouse as, incredibly and totally unexpected, it shares approximately 70% of the same protein-coding gene sequences with us.&nbsp;<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.genoway.com\/data\/fichiers\/file\/contenu\/products-services\/custom-models\/knockout\/schemes\/constitutive-knockout-mouse\" alt=\"\" width=\"755\" height=\"232\" \/><\/figure><\/div>\n\n\n<h2 class=\"has-text-align-center wp-block-heading\"><strong>How do we make a knockout mouse?<\/strong><\/h2>\n\n\n\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<iframe loading=\"lazy\" title=\"What is a knockout mouse?\" width=\"500\" height=\"281\" src=\"https:\/\/www.youtube.com\/embed\/BGDqhO0eHys?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share\" referrerpolicy=\"strict-origin-when-cross-origin\" allowfullscreen><\/iframe>\n<\/div><\/figure>\n\n\n\n<p class=\"has-text-align-center\">Although knockout mice are very useful tools, they still have their disadvantages:<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li>Genetic engineering is a difficult, expensive and time-consuming<\/li><li>Unethical issues due to the use of animals for scientific research&nbsp;<\/li><li>Although the degree of gene homology is enormous between mice and humans, there are still genes that could have a certain function in laboratory animals but not the same function in humans<\/li><\/ol>\n\n\n\n<p>Absent or non functional proteins are the cause of more than half of human\u2019s diseases. This is why knockout animals are so important for biomedical research. Once the function of a gene is known, researchers can work on developing a range of drugs to treat the disease, such as drugs that replicate the function of the missing protein or drugs that mitigate the effects of the disease.<\/p>\n\n\n\n<h2 class=\"has-text-align-center wp-block-heading\"><strong>Conclusion<\/strong><\/h2>\n\n\n\n<p>Last year during university lectures, I had heard for the first time the term \u201cknockout\u201d without having a clue of what it was. In the first lecture of this new module, Engineering Replacement Body Parts, I was explicitly introduced to this concept for the first time.&nbsp;<\/p>\n\n\n\n<p>My interest to research and expand knowledge on this methodology was that I had found this concept completely counterintuitive, as it works in a \u201creversed\u201d manner! The principle is that we cannot study directly what the gene encodes if it is functional but we can infer its function when its final product, the protein, is no longer functional or completely absent.&nbsp;<\/p>\n\n\n\n<p>Initially, I thought that scientists were always able to \u201cisolate\u201d the molecule of interest and then test it under a range of conditions in order to discover their properties and functions.&nbsp;This assumption was harshly challenged by the fact that, unfortunately, isolation of molecules is rarely achievable for a series of obstacles, such as lack of powerful enough technology or extremely high costs. For instance, we cannot visualise \u201cin real time\u201d the action of very tiny cellular components, such as nucleic acids, but we can do it for larger entities like living bacteria under a microscope.&nbsp;<\/p>\n\n\n\n<p>I realised that something, which could immediately appear as counterintuitive, is not necessarily extremely complicated to understand. In the future, I will not feel discouraged if I cannot instantly catch a counterintuitive principle or technique, as this could reveal it as extremely important! Deepening my knowledge of knockout revolutionised my understanding of an essential scientific methodology used worldwide to discover the cause of many genetic diseases. As a future biomedical scientist, I will apply this knowledge to real-world scenarios not only to perfectly understand and review others\u2019 research but also to design my future experiments and discover the cause of some human diseases!<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">Reference<\/h4>\n\n\n\n<p>National Human Genome Research Institute: <a href=\"https:\/\/www.genome.gov\/genetics-glossary\/Knockout\">https:\/\/www.genome.gov\/genetics-glossary\/Knockout<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The human genome is \u201cpacked\u201d in a particular molecule called DNA, which composes the core of our cells. This molecule is extremely big; if we could completely stretch it, it would be 2 metres long!&nbsp; This incredible molecule, DNA, is composed of 2 main regions: coding and non-coding regions. The non-coding region is significantly more [&hellip;]<\/p>\n","protected":false},"author":5518,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-8012","post","type-post","status-publish","format-standard","hentry","category-uncategorised"],"jetpack_featured_media_url":"","_links":{"self":[{"href":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/wp-json\/wp\/v2\/posts\/8012","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/wp-json\/wp\/v2\/users\/5518"}],"replies":[{"embeddable":true,"href":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/wp-json\/wp\/v2\/comments?post=8012"}],"version-history":[{"count":7,"href":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/wp-json\/wp\/v2\/posts\/8012\/revisions"}],"predecessor-version":[{"id":8640,"href":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/wp-json\/wp\/v2\/posts\/8012\/revisions\/8640"}],"wp:attachment":[{"href":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/wp-json\/wp\/v2\/media?parent=8012"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/wp-json\/wp\/v2\/categories?post=8012"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/generic.wordpress.soton.ac.uk\/uosm2031\/wp-json\/wp\/v2\/tags?post=8012"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}