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Genome editing , or genome engineering , or gene editing , is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases ( FokI and Cas ), and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ).

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130-858: BE3 may refer to: The BE3 Base Editor BE-3 , a rocket engine from Blue Origin Royal Aircraft Factory B.E.3 , a 1912 aircraft Bracuí (D-23, U-31, Be-3), a Brazilian destroyer escort warship previously known as USS Reybold (DE-177) Virgin Media Three , a television channel within the Republic of Ireland formally known as be3. BE3 (#BE3), shortcut for Bethesda + E3 , hashtag for Bethesda 's panel on Electronic Entertainment Expo The EU NUTS I statistical region denoting Wallonia in Belgium [REDACTED] Topics referred to by

260-459: A vector with the desired genetic elements within a sequence that is homologous to the flanking sequences of a DSB. This will result in the desired change being inserted at the site of the DSB. While HDR based gene editing is similar to the homologous recombination based gene targeting, the rate of recombination is increased by at least three orders of magnitude. The key to genome editing is creating

390-449: A CRISPR alternative, labeled obligate mobile element–guided activity (OMEGA) proteins including IscB, IsrB and TnpB as endonucleases found in transposons , and guided by small ωRNAs. Genetic engineering as method of introducing new genetic elements into organisms has been around since the 1970s. One drawback of this technology has been the random nature with which the DNA is inserted into

520-474: A DSB at a specific point within the genome. Commonly used restriction enzymes are effective at cutting DNA, but generally recognize and cut at multiple sites. To overcome this challenge and create site-specific DSB, three distinct classes of nucleases have been discovered and bioengineered to date. These are the Zinc finger nucleases ( ZFNs ), transcription-activator like effector nucleases ( TALEN ), meganucleases and

650-525: A Faculty of Law in 1707, a Faculty of Arts in 1708, and a Faculty of Medicine in 1726. In 1762, Reverend Hugh Blair was appointed by King George III as the first Regius Professor of Rhetoric and Belles-Lettres . This formalised literature as a subject and marks the foundation of the English Literature department, making Edinburgh the oldest centre of literary education in Britain. During

780-590: A conserved amino acid sequence . Meganucleases, found commonly in microbial species, have the unique property of having very long recognition sequences (>14bp) thus making them naturally very specific. However, there is virtually no chance of finding the exact meganuclease required to act on a chosen specific DNA sequence. To overcome this challenge, mutagenesis and high throughput screening methods have been used to create meganuclease variants that recognize unique sequences. Others have been able to fuse various meganucleases and create hybrid enzymes that recognize

910-400: A functional gene into an organism and targeting it to replace the defective one it could be possible to cure certain genetic diseases . Early methods to target genes to certain sites within a genome of an organism (called gene targeting ) relied on homologous recombination (HR). By creating DNA constructs that contain a template that matches the targeted genome sequence it is possible that

1040-724: A government visitation in 1690. The university was subsequently led by Principal Gilbert Rule , one of the inquisitors on the visitation committee. "You are now in a place where the best courses upon earth are within your reach... Such an opportunity you will never again have. I would therefore strongly press on you to fix no other limit to your stay in Edinborough than your having got thro this whole course. The omission of any one part of it will be an affliction & loss to you as long as you live." Thomas Jefferson , writing to his son-in-law Thomas Mann Randolph, Jr. in 1786. The late 17th and early 18th centuries were marked by

1170-469: A higher number of target sites with high precision. New TALE nucleases take about one week and a few hundred dollars to create, with specific expertise in molecular biology and protein engineering. CRISPR nucleases have a slightly lower precision when compared to the TALE nucleases. This is caused by the need of having a specific nucleotide at one end in order to produce the guide RNA that CRISPR uses to repair

1300-485: A highly conserved sequence of 34 amino acids, and recognize a single DNA nucleotide within the target site. The nuclease can create double strand breaks at the target site that can be repaired by error-prone non-homologous end-joining (NHEJ), resulting in gene disruptions through the introduction of small insertions or deletions. Each repeat is conserved, with the exception of the so-called repeat variable di-residues (RVDs) at amino acid positions 12 and 13. The RVDs determine

1430-733: A leading intellectual centre during the Scottish Enlightenment and contributed to the city being nicknamed the " Athens of the North ". The three main global university rankings ( ARWU , THE , and QS ) place the University of Edinburgh within their respective top 40. It is a member of several associations of research-intensive universities, including the Coimbra Group , League of European Research Universities , Russell Group , Una Europa , and Universitas 21 . In

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1560-423: A matter of days. MAGE experiments can be divided into three classes, characterized by varying degrees of scale and complexity: (i) many target sites, single genetic mutations; (ii) single target site, many genetic mutations; and (iii) many target sites, many genetic mutations. An example of class three was reflected in 2009, where Church and colleagues were able to program Escherichia coli to produce five times

1690-602: A new sequence. Yet others have attempted to alter the DNA interacting aminoacids of the meganuclease to design sequence specific meganucelases in a method named rationally designed meganuclease. Another approach involves using computer models to try to predict as accurately as possible the activity of the modified meganucleases and the specificity of the recognized nucleic sequence. A large bank containing several tens of thousands of protein units has been created. These units can be combined to obtain chimeric meganucleases that recognize

1820-418: A new tool, further increasing the range of methods available . In particular CRISPR/Cas9 engineered endonucleases allows the use of multiple guide RNAs for simultaneous Knockouts (KO) in one step by cytoplasmic direct injection (CDI) on mammalian zygotes. Furthermore, gene editing can be applied to certain types of fish in aquaculture such as Atlantic salmon. Gene editing in fish is currently experimental, but

1950-685: A partnership with the Centre for Genomic & Experimental Medicine and the ECRC to create the Institute of Genetics and Molecular Medicine (renamed the Institute of Genetics and Cancer in 2021) on the same site. In April 2008, the Roslin Institute – an animal sciences research centre known for cloning Dolly the sheep – became part of the Royal (Dick) School of Veterinary Studies. In 2011,

2080-399: A power struggle between the university and town council, which had ultimate authority over staff appointments, curricula, and examinations. After a series of challenges by the university, the conflict culminated in the council seizing the college records in 1704. Relations were only gradually repaired over the next 150 years and suffered repeated setbacks. The university expanded by founding

2210-484: A range of genomes, in particular by the laboratories in the Zinc Finger Consortium. The US company Sangamo BioSciences uses zinc finger nucleases to carry out research into the genetic engineering of stem cells and the modification of immune cells for therapeutic purposes. Modified T lymphocytes are currently undergoing phase I clinical trials to treat a type of brain tumor ( glioblastoma ) and in

2340-491: A result, high degrees of expertise and lengthy and costly validations processes are required. TALE nucleases being the most precise and specific method yields a higher efficiency than the previous two methods. It achieves such efficiency because the DNA-binding element consists of an array of TALE subunits, each of them having the capability of recognizing a specific DNA nucleotide chain independent from others, resulting in

2470-600: A series of corridors. The Easter Bush campus, located seven miles south of the city, houses the Jeanne Marchig International Centre for Animal Welfare Education, Roslin Institute , Royal (Dick) School of Veterinary Studies, and Veterinary Oncology and Imaging Centre. The Roslin Institute is an animal sciences research institute which is sponsored by BBSRC . The Institute won international fame in 1996, when its researchers Sir Ian Wilmut , Keith Campbell and their colleagues created Dolly

2600-738: A similar way, with the Flip recombinase recognising FRT sequences. By crossing an organism containing the recombinase sites flanking the gene of interest with an organism that express the SSR under control of tissue specific promoters , it is possible to knock out or switch on genes only in certain cells. These techniques were also used to remove marker genes from transgenic animals. Further modifications of these systems allowed researchers to induce recombination only under certain conditions, allowing genes to be knocked out or expressed at desired times or stages of development . A common form of Genome editing relies on

2730-467: A single regent; and the lack of land endowments as its source of income, which meant its faculty operated in a more competitive environment. Between 1750 and 1800, this system produced and attracted key Enlightenment figures such as chemist Joseph Black , economist Adam Smith , historian William Robertson , philosophers David Hume and Dugald Stewart , physician William Cullen , and early sociologist Adam Ferguson , many of which taught concurrently. By

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2860-631: A small kitchen table. Those mutations combine with the variation that naturally occurs during cell mitosis creating billions of cellular mutations. Chemically combined, synthetic single-stranded DNA (ssDNA) and a pool of oligionucleotides are introduced at targeted areas of the cell thereby creating genetic modifications. The cyclical process involves transformation of ssDNA (by electroporation ) followed by outgrowth, during which bacteriophage homologous recombination proteins mediate annealing of ssDNAs to their genomic targets. Experiments targeting selective phenotypic markers are screened and identified by plating

2990-424: A unique DNA sequence. To enhance this effect, FokI nucleases have been engineered that can only function as heterodimers. Several approaches are used to design specific zinc finger nucleases for the chosen sequences. The most widespread involves combining zinc-finger units with known specificities (modular assembly). Various selection techniques, using bacteria, yeast or mammal cells have been developed to identify

3120-540: A university court and a general council, and redefined the roles of key officials like the chancellor, rector, and principal. The Edinburgh Seven were the first group of matriculated undergraduate female students at any British university. Led by Sophia Jex-Blake , they began studying medicine at the University of Edinburgh in 1869. Although the university blocked them from graduating and qualifying as doctors, their campaign gained national attention and won them many supporters, including Charles Darwin . Their efforts put

3250-464: A variety of nucleic acid interacting proteins such as transcription factors . Each finger of the Zinc finger domain is completely independent and the binding capacity of one finger is impacted by its neighbor. TALEs on the other hand are found in repeats with a one-to-one recognition ratio between the amino acids and the recognized nucleotide pairs. Because both zinc fingers and TALEs happen in repeated patterns, different combinations can be tried to create

3380-654: A wide variety of sequence specificities. Zinc fingers have been more established in these terms and approaches such as modular assembly (where Zinc fingers correlated with a triplet sequence are attached in a row to cover the required sequence), OPEN (low-stringency selection of peptide domains vs. triplet nucleotides followed by high-stringency selections of peptide combination vs. the final target in bacterial systems), and bacterial one-hybrid screening of zinc finger libraries among other methods have been used to make site specific nucleases. Zinc finger nucleases are research and development tools that have already been used to modify

3510-583: Is a public research university based in Edinburgh , Scotland . Founded by the town council under the authority of a royal charter from King James VI in 1582 and officially opened in 1583, it is one of Scotland's four ancient universities and the sixth-oldest university in continuous operation in the English-speaking world . The university played a crucial role in Edinburgh becoming

3640-424: Is a need for reliable design and subsequent test of the nucleases, the absence of toxicity of the nucleases, the appropriate choice of the plant tissue for targeting, the routes of induction of enzyme activity, the lack of off-target mutagenesis , and a reliable detection of mutated cases. A common delivery method for CRISPR/Cas9 in plants is Agrobacterium -based transformation. T-DNA is introduced directly into

3770-415: Is advantageous over a virally delivered gene as there is no need to include the full coding sequences and regulatory sequences when only a small proportions of the gene needs to be altered as is often the case. The expression of the partially replaced genes is also more consistent with normal cell biology than full genes that are carried by viral vectors. The first clinical use of TALEN-based genome editing

3900-401: Is based on an easy-to-predict code. TAL nucleases are specific to their target due in part to the length of their 30+ base pairs binding site. TALEN can be performed within a 6 base pairs range of any single nucleotide in the entire genome. TALEN constructs are used in a similar way to designed zinc finger nucleases, and have three advantages in targeted mutagenesis: (1) DNA binding specificity

4030-544: Is different from Wikidata All article disambiguation pages All disambiguation pages Base Editors Genome editing was pioneered in the 1990s, before the advent of the common current nuclease-based gene editing platforms but its use was limited by low efficiencies of editing. Genome editing with engineered nucleases, i.e. all three major classes of these enzymes—zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and engineered meganucleases—were selected by Nature Methods as

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4160-461: Is exposed to UV rays. Meganucleases have the benefit of causing less toxicity in cells than methods such as Zinc finger nuclease (ZFN), likely because of more stringent DNA sequence recognition; however, the construction of sequence-specific enzymes for all possible sequences is costly and time-consuming, as one is not benefiting from combinatorial possibilities that methods such as ZFNs and TALEN-based fusions utilize. As opposed to meganucleases,

4290-595: Is higher, (2) off-target effects are lower, and (3) construction of DNA-binding domains is easier. CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) are genetic elements that bacteria use as a kind of acquired immunity to protect against viruses. They consist of short sequences that originate from viral genomes and have been incorporated into the bacterial genome. Cas (CRISPR associated proteins) process these sequences and cut matching viral DNA sequences. By introducing plasmids containing Cas genes and specifically constructed CRISPRs into eukaryotic cells,

4420-693: Is likely to benefit from the ability of engineered nuclease to add or remove genomic elements and therefore create complex systems. In addition, gene functions can be studied using stem cells with engineered nucleases. Listed below are some specific tasks this method can carry out: The combination of recent discoveries in genetic engineering, particularly gene editing and the latest improvement in bovine reproduction technologies (e.g. in vitro embryo culture) allows for genome editing directly in fertilised oocytes using synthetic highly specific endonucleases. RNA-guided endonucleases:clustered regularly interspaced short palindromic repeats associated Cas9 (CRISPR/Cas9) are

4550-709: Is located nearby, as is Edinburgh College of Art in Lauriston . North of George Square lies the university's Old College housing Edinburgh Law School , New College on The Mound housing the School of Divinity, and St Cecilia's Hall . Some of these buildings are used to host events during the Edinburgh International Festival and the Edinburgh Festival Fringe every summer. Pollock Halls, adjoining Holyrood Park to

4680-431: Is most often located at the protein-DNA interaction sites, where it stabilizes the motif. The C-terminal part of each finger is responsible for the specific recognition of the DNA sequence. The recognized sequences are short, made up of around 3 base pairs, but by combining 6 to 8 zinc fingers whose recognition sites have been characterized, it is possible to obtain specific proteins for sequences of around 20 base pairs. It

4810-470: Is only appropriate for precise editing requiring single nucleotide changes and has found to be highly efficient for this type of editing. ARCUT stands for artificial restriction DNA cutter, it is a technique developed by Komiyama. This method uses pseudo-complementary peptide nucleic acid (pcPNA), for identifying cleavage site within the chromosome. Once pcPNA specifies the site, excision is carried out by cerium (CE) and EDTA (chemical mixture), which performs

4940-538: Is the eighth-largest university in the UK by enrolment and receives over 69,000 undergraduate applications per year, making it the third-most popular university in the UK by application volume. In 2021, Edinburgh had the seventh-highest average UCAS points among British universities for new entrants. The university maintains strong links to the royal family , with Prince Philip, Duke of Edinburgh , serving as its chancellor from 1953 to 2010, and Anne, Princess Royal , holding

5070-484: Is the university's governing body and the legal person of the university, chaired by the rector and consisting of the principal, Lord Provost of Edinburgh , and of Assessors appointed by the rector, chancellor, Edinburgh Town Council , General Council, and Senatus Academicus . By the Universities (Scotland) Act 1889, it is a body corporate, with perpetual succession and a common seal. All property belonging to

5200-538: Is therefore possible to control the expression of a specific gene. It has been demonstrated that this strategy can be used to promote a process of angiogenesis in animals. It is also possible to fuse a protein constructed in this way with the catalytic domain of an endonuclease in order to induce a targeted DNA break, and therefore to use these proteins as genome engineering tools. The method generally adopted for this involves associating two DNA binding proteins – each containing 3 to 6 specifically chosen zinc fingers – with

5330-905: The Edinburgh Cowgate fire destroyed a number of university buildings, including some 3,000 m (32,000 sq ft) of the School of Informatics at 80 South Bridge . This was replaced with the Informatics Forum on Bristo Square , completed in July 2008. Also in 2002, the Edinburgh Cancer Research Centre (ECRC) was opened on the Western General Hospital site. In 2007, the MRC Human Genetics Unit formed

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5460-665: The Joseph Black Building), housing the Department of Chemistry . The campus was named King's Buildings in honour of George V. New College on The Mound was originally opened in 1846 as a Free Church of Scotland college, later of the United Free Church of Scotland . Since the 1930s it has been the home of the School of Divinity. Prior to the 1929 reunion of the Church of Scotland , candidates for

5590-734: The Little France area of Edinburgh. The new campus was named the BioQuarter . The Chancellor's Building was opened on 12 August 2002 by Prince Philip , housing the new Edinburgh Medical School alongside the new Royal Infirmary of Edinburgh. In 2007, the campus saw the addition of the Euan MacDonald Centre as a research centre for motor neuron diseases , which was part-funded by Scottish entrepreneur Euan MacDonald and his father Donald. In August 2010, author J. K. Rowling provided £10 million in funding to create

5720-640: The School of Chemistry ), Royal Observatory , Swann Building (the Wellcome Trust Centre for Cell Biology), Waddington Building (the Centre for Systems Biology at Edinburgh), William Rankine Building (School of Engineering's Institute for Infrastructure and Environment), and others. Until 2012, the KB campus was served by three libraries: Darwin Library, James Clerk Maxwell Library, and Robertson Engineering and Science Library. These were replaced by

5850-592: The Senatus is to regulate and supervise the teaching and discipline of the university and to promote research. The Senatus elects four Assessors on the University Court. The Senatus meets three times per year, hosting a presentation and discussion session which is open to all members of staff at each meeting. The university's three most significant officials are its chancellor, rector, and principal, whose rights and responsibilities are largely derived from

5980-479: The fiscal year ending 31 July 2023, the university had a total income of £1.341 billion, with £339.5 million from research grants and contracts. It has the third-largest endowment in the UK, behind only Cambridge and Oxford . The university occupies five main campuses in the city of Edinburgh, which include many buildings of historical and architectural significance, such as those in the Old Town . Edinburgh

6110-512: The 18th century, the university developed a particular forte in teaching anatomy and the developing science of surgery , and it was considered one of the best medical schools in the English-speaking world. Bodies to be used for dissection were brought to the university's Anatomy Theatre through a secret tunnel from a nearby house (today's College Wynd student accommodation), which was also used by murderers Burke and Hare to deliver

6240-498: The 18th century, the university was at the centre of the Scottish Enlightenment . The ideas of the Age of Enlightenment fell on especially fertile ground in Edinburgh because of the university's democratic and secular origin; its organization as a single entity instead of loosely connected colleges, which encouraged academic exchange; its adoption of the more flexible Dutch model of professorship, rather than having student cohorts taught by

6370-467: The 19th century, Old College was becoming overcrowded. After a bequest from Sir David Baxter , the university started planning new buildings in earnest. Sir Robert Rowand Anderson won the public architectural competition and was commissioned to design new premises for the Medical School in 1877. Initially, the design incorporated a campanile and a hall for examination and graduation, but this

6500-492: The 2007 Nobel Prize for Physiology or Medicine . If a vital gene is knocked out it can prove lethal to the organism. In order to study the function of these genes site specific recombinases (SSR) were used. The two most common types are the Cre-LoxP and Flp-FRT systems. Cre recombinase is an enzyme that removes DNA by homologous recombination between binding sequences known as Lox-P sites. The Flip-FRT system operates in

6630-498: The 2011 Method of the Year. The CRISPR-Cas system was selected by Science as 2015 Breakthrough of the Year. As of 2015 four families of engineered nucleases were used: meganucleases , zinc finger nucleases (ZFNs), transcription activator-like effector-based nucleases (TALEN), and the clustered regularly interspaced short palindromic repeats ( CRISPR / Cas9 ) system. Nine genome editors were available as of 2017 . In 2018,

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6760-699: The 2020s was the conversion of some of the historic Royal Infirmary of Edinburgh buildings in Lauriston Place, which had been vacated in 2003 and partially developed into the Quartermile . The £120 million project created a home for the Edinburgh Futures Institute (EFI), an interdisciplinary hub linking arts, humanities, and social sciences with other disciplines in the research and teaching of complex, multi-stakeholder societal challenges. The EFI officially opened its doors to

6890-533: The 79th regiment to be called from Edinburgh Castle to quell the disturbance. This was later immortalised in a 92-page humorous account written by the students entitled The University Snowdrop and then later, in 1853, in a landscape by English artist, Samuel Bough . After 275 years of governance by the town council, the Universities (Scotland) Act 1858 gave the university full authority over its own affairs. The act established governing bodies including

7020-717: The Anne Rowling Regenerative Neurology Clinic, which was officially opened in October 2013. The Centre for Regenerative Medicine (CRM) is a stem cell research centre dedicated to the development of regenerative treatments, which was opened in 2012. CRM is also home to applied scientists working with the Scottish National Blood Transfusion Service (SNBTS) and Roslin Cells. In December 2002,

7150-595: The CRISPR based genome editing tool has made it feasible to disrupt or remove key genes in order to elucidate function in a human setting. Genome editing using Meganuclease , ZFNs, and TALEN provides a new strategy for genetic manipulation in plants and are likely to assist in the engineering of desired plant traits by modifying endogenous genes. For instance, site-specific gene addition in major crop species can be used for 'trait stacking' whereby several desired traits are physically linked to ensure their co-segregation during

7280-794: The College of Arts, Humanities and Social Sciences and the School of Informatics . The highest concentration of university buildings is around George Square , which includes 40 George Square (formerly David Hume Tower), Appleton Tower , Main Library , and Gordon Aikman Lecture Theatre , the area's largest lecture hall. Around nearby Bristo Square lie the Dugald Stewart Building , Informatics Forum , McEwan Hall , Potterrow Student Centre , Teviot Row House , and old Medical School , which still houses pre-clinical medical courses and biomedical sciences. The Pleasance , one of Edinburgh University Students' Association 's main buildings,

7410-611: The DNA sequence to which the TALE will bind. This simple one-to-one correspondence between the TALE repeats and the corresponding DNA sequence makes the process of assembling repeat arrays to recognize novel DNA sequences straightforward. These TALEs can be fused to the catalytic domain from a DNA nuclease, FokI, to generate a transcription activator-like effector nuclease (TALEN). The resultant TALEN constructs combine specificity and activity, effectively generating engineered sequence-specific nucleases that bind and cleave DNA sequences only at pre-selected sites. The TALEN target recognition system

7540-609: The HR processes within the cell will insert the construct at the desired location. Using this method on embryonic stem cells led to the development of transgenic mice with targeted genes knocked out . It has also been possible to knock in genes or alter gene expression patterns. In recognition of their discovery of how homologous recombination can be used to introduce genetic modifications in mice through embryonic stem cells, Mario Capecchi , Martin Evans and Oliver Smithies were awarded

7670-700: The National Robotarium. The deal also included creation of the Edinburgh International Data Facility, which performs high-speed data processing in a secure environment. In September 2020, the university completed work on the Richard Verney Health Centre at its central area campus on Bristo Square. The facility houses a health centre and pharmacy, and the university's disability and counselling services. The university's largest expansion in

7800-597: The Noreen and Kenneth Murray Library opened for the academic year 2012/13. The campus also hosts the National e-Science Centre (NeSC), Scotland's Rural College (SRUC), Scottish Institute for Enterprise (SIE), Scottish Microelectronics Centre (SMC), and Scottish Universities Environmental Research Centre (SUERC). The BioQuarter campus, based in the Little France area, is home to the majority of medical facilities of

7930-647: The Pacific Chinook salmon and a promoter sequence from the ocean pout Thanks to the parallel development of single-cell transcriptomics, genome editing and new stem cell models we are now entering a scientifically exciting period where functional genetics is no longer restricted to animal models but can be performed directly in human samples. Single-cell gene expression analysis has resolved a transcriptional road-map of human development from which key candidate genes are being identified for functional studies. Using global transcriptomics data to guide experimentation,

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8060-652: The Polish School of Medicine is located in the Quadrangle of the old Medical School in Teviot Place. On 10 May 1951, the Royal (Dick) Veterinary College , founded in 1823 by William Dick , was reconstituted as the Royal (Dick) School of Veterinary Studies and officially became part of the university. It achieved full faculty status as Faculty of Veterinary Medicine in 1964. In 1955 the university opened

8190-463: The Science and Medicine buildings had suffered from a lack of repairs or upgrades, which was exacerbated by an influx of students after the end of the war. In 1919, the university bought the land of West Mains Farm in the south of the city for the development of a new satellite campus specialising in the sciences. On 6 July 1920, King George V laid the foundation of the first new building (now called

8320-575: The UK and Scottish governments, six local authorities and all universities and colleges in the region. The university committed to delivering a range of economic benefits to the region through the Data-Driven Innovation initiative. In conjunction with Heriot-Watt University , the deal created five innovation hubs: the Bayes Centre, Edinburgh Futures Institute, Usher Institute, Easter Bush, and one further hub based at Heriot-Watt,

8450-511: The Universities (Scotland) Act 1858. The office of chancellor serves as the titular head and highest office of the university. Their duties include conferring degrees and enhancing the profile and reputation of the university on national and global levels. The chancellor is elected by the university's General Council , and a person generally remains in the office for life. Previous chancellors include former prime minister Arthur Balfour and novelist Sir J. M. Barrie . Princess Anne has held

8580-616: The area's historic houses and erecting modern buildings such as 40 George Square , Appleton Tower and the Main Library . On 1 August 1998, the Moray House Institute of Education , founded in 1848, merged with the University of Edinburgh, becoming its Faculty of Education. Following the internal restructuring of the university in 2002, Moray House became known as the Moray House School of Education . It

8710-480: The breeding processes. Progress in such cases have been recently reported in Arabidopsis thaliana and Zea mays . In Arabidopsis thaliana , using ZFN-assisted gene targeting, two herbicide-resistant genes (tobacco acetolactate synthase SuRA and SuRB) were introduced to SuR loci with as high as 2% transformed cells with mutations. In Zea mays, disruption of the target locus was achieved by ZFN-induced DSBs and

8840-492: The catalytic domain of the FokI endonuclease which need to dimerize to cleave the double-strand DNA. The two proteins recognize two DNA sequences that are a few nucleotides apart. Linking the two zinc finger proteins to their respective sequences brings the two FokI domains closer together. FokI requires dimerization to have nuclease activity and this means the specificity increases dramatically as each nuclease partner would recognize

8970-456: The cells on differential medias. Each cycle ultimately takes 2.5 hours to process, with additional time required to grow isogenic cultures and characterize mutations. By iteratively introducing libraries of mutagenic ssDNAs targeting multiple sites, MAGE can generate combinatorial genetic diversity in a cell population. There can be up to 50 genome edits, from single nucleotide base pairs to whole genome or gene networks simultaneously with results in

9100-510: The city. Most of the Science and Engineering College's research and teaching activities take place at the campus, which occupies a 35-hectare site. It includes the Alexander Graham Bell Building (for mobile phones and digital communications systems), James Clerk Maxwell Building (the administrative and teaching centre of the School of Physics and Astronomy and School of Mathematics), Joseph Black Building (home to

9230-461: The clustered regularly interspaced short palindromic repeats ( CRISPR /Cas9) system. Meganucleases , discovered in the late 1980s, are enzymes in the endonuclease family which are characterized by their capacity to recognize and cut large DNA sequences (from 14 to 40 base pairs). The most widespread and best known meganucleases are the proteins in the LAGLIDADG family, which owe their name to

9360-508: The combinations that offer the best specificity and the best cell tolerance. Although the direct genome-wide characterization of zinc finger nuclease activity has not been reported, an assay that measures the total number of double-strand DNA breaks in cells found that only one to two such breaks occur above background in cells treated with zinc finger nucleases with a 24 bp composite recognition site and obligate heterodimer FokI nuclease domains. The heterodimer functioning nucleases would avoid

9490-473: The common methods for such editing used engineered nucleases , or "molecular scissors". These nucleases create site-specific double-strand breaks (DSBs) at desired locations in the genome. The induced double-strand breaks are repaired through nonhomologous end-joining (NHEJ) or homologous recombination (HR), resulting in targeted mutations ('edits'). In May 2019, lawyers in China reported, in light of

9620-458: The concept behind ZFNs and TALEN technology is based on a non-specific DNA cutting catalytic domain, which can then be linked to specific DNA sequence recognizing peptides such as zinc fingers and transcription activator-like effectors (TALEs). The first step to this was to find an endonuclease whose DNA recognition site and cleaving site were separate from each other, a situation that is not the most common among restriction enzymes. Once this enzyme

9750-412: The concept of DNA double stranded break (DSB) repair mechanics. There are two major pathways that repair DSB; non-homologous end joining (NHEJ) and homology directed repair (HDR). NHEJ uses a variety of enzymes to directly join the DNA ends while the more accurate HDR uses a homologous sequence as a template for regeneration of missing DNA sequences at the break point. This can be exploited by creating

9880-470: The corpses of their victims during the 1820s. The Edinburgh snowball riots of 1838 also known as the ' Wars of the Quadrangle ' occurred when University of Edinburgh students engaged in what started as a snowball fight in "a spirit of harmless amusement" before becoming a two-day 'battle' at Old College with local Edinburgh residents on South Bridge which led to the Lord Provost calling from

10010-572: The double-strand break it induces. It has been shown to be the quickest and cheapest method, only costing less than two hundred dollars and a few days of time. CRISPR also requires the least amount of expertise in molecular biology as the design lays in the guide RNA instead of the proteins. One major advantage that CRISPR has over the ZFN and TALEN methods is that it can be directed to target different DNA sequences using its ~80nt CRISPR sgRNAs, while both ZFN and TALEN methods required construction and testing of

10140-418: The east, is the university's largest residence hall for undergraduate students in their first year. The complex houses over 2,000 students during term time and consists of ten named buildings with communal green spaces between them. The two original buildings, St Leonard's Hall and Salisbury Green , were built in the 19th century, while the majority of Pollock Halls dates from the 1960s and early 2000s. Two of

10270-531: The endogenous banana streak virus in the B genome of banana ( Musa spp. ) to overcome a major challenge in banana breeding. In addition, TALEN-based genome engineering has been extensively tested and optimized for use in plants. TALEN fusions have also been used by a U.S. food ingredient company, Calyxt, to improve the quality of soybean oil products and to increase the storage potential of potatoes Several optimizations need to be made in order to improve editing plant genomes using ZFN-mediated targeting. There

10400-459: The eukaryotic genome can be cut at any desired position. One of the earliest methods of efficiently editing nucleic acids employs nucleobase modifying enzymes directed by nucleic acid guide sequences was first described in the 1990s and has seen resurgence more recently. This method has the advantage that it does not require breaking the genomic DNA strands, and thus avoids the random insertion and deletions associated with DNA strand breakage. It

10530-831: The fight against AIDS. Transcription activator-like effector nucleases (TALENs) are specific DNA-binding proteins that feature an array of 33 or 34-amino acid repeats. TALENs are artificial restriction enzymes designed by fusing the DNA cutting domain of a nuclease to TALE domains, which can be tailored to specifically recognize a unique DNA sequence. These fusion proteins serve as readily targetable "DNA scissors" for gene editing applications that enable to perform targeted genome modifications such as sequence insertion, deletion, repair and replacement in living cells. The DNA binding domains, which can be designed to bind any desired DNA sequence, comes from TAL effectors , DNA-binding proteins excreted by plant pathogenic Xanthomanos app. TAL effectors consists of repeated domains, each of which contains

10660-559: The first department of nursing in Europe for academic study. This department was inspired by the work of Gladys Beaumont Carter and a grant from the Rockefeller Foundation . By the end of the 1950s, there were around 7,000 students matriculating annually, more than doubling the numbers from the turn of the century. The university addressed this partially through the redevelopment of George Square , demolishing much of

10790-416: The first ever "in body" human gene editing therapy to permanently alter DNA - in a patient with Hunter syndrome . Clinical trials by Sangamo involving gene editing using Zinc Finger Nuclease (ZFN) are ongoing. University of Edinburgh The University of Edinburgh ( Scots : University o Edinburgh , Scottish Gaelic : Oilthigh Dhùn Èideann ; abbreviated as Edin. in post-nominals )

10920-399: The former principal of the university Sir Timothy O'Shea and was opened by Princess Anne in 2017, providing a living and social environment for postgraduate students. The Outreach Centre, Institute for Academic Development (University Services Group), and Edinburgh Centre for Professional Legal Studies are also located at Holyrood. The King's Buildings campus is located in the south of

11050-528: The genome one little section at a time, observe the phenotype, and start the process over with a different single-gene manipulation. Therefore, researchers at the Wyss Institute at Harvard University designed the MAGE, a powerful technology that improves the process of in vivo genome editing. It allows for quick and efficient manipulations of a genome, all happening in a machine small enough to put on top of

11180-449: The greatest efficiency and fewer off-target effects. Based on the maximum theoretical distance between DNA binding and nuclease activity, TALEN approaches result in the greatest precision. The methods for scientists and researchers wanting to study genomic diversity and all possible associated phenotypes were very slow, expensive, and inefficient. Prior to this new revolution, researchers would have to do single-gene manipulations and tweak

11310-434: The hosts genome , which can impair or alter other genes within the organism. Although, several methods have been discovered which target the inserted genes to specific sites within an organism genome. It has also enabled the editing of specific sequences within a genome as well as reduced off target effects. This could be used for research purposes, by targeting mutations to specific genes, and in gene therapy . By inserting

11440-473: The improvements in TALEN-based approaches testify to the significance of the methods, and the list is expanding rapidly. Genome editing with engineered nucleases will likely contribute to many fields of life sciences from studying gene functions in plants and animals to gene therapy in humans. For instance, the field of synthetic biology which aims to engineer cells and organisms to perform novel functions,

11570-508: The manufacturing and production of important compounds in the bioengineering, bioenergy, biomedical engineering, synthetic biology, pharmaceutical, agricultural, and chemical industries. As of 2012 efficient genome editing had been developed for a wide range of experimental systems ranging from plants to animals, often beyond clinical interest, and was becoming a standard experimental strategy in research labs. The recent generation of rat, zebrafish , maize and tobacco ZFN-mediated mutants and

11700-652: The ministry in the United Free Church studied at New College, whilst candidates for the Church of Scotland studied in the university's Faculty of Divinity. In 1935 the two institutions merged, with all operations moved to the New College site in Old Town. This freed up Old College for Edinburgh Law School . The Polish School of Medicine was established in 1941 as a wartime academic initiative. While it

11830-494: The normal amount of lycopene, an antioxidant normally found in tomato seeds and linked to anti-cancer properties. They applied MAGE to optimize the 1-deoxy- D -xylulose 5-phosphate (DXP) metabolic pathway in Escherichia coli to overproduce isoprenoid lycopene. It took them about 3 days and just over $ 1,000 in materials. The ease, speed, and cost efficiency in which MAGE can alter genomes can transform how industries approach

11960-632: The older houses in Pollock Halls were demolished in 2002, and a new building, Chancellor's Court, was built in their place and opened in 2003. Self-catered flats elsewhere account for the majority of university-provided accommodation. The area also includes the John McIntyre Conference Centre opened in 2009, which is the university's premier conference space. The Holyrood campus, just off the Royal Mile , used to be

12090-620: The other ancient universities of Scotland , and in contrast to nearly all other pre-1992 universities which are established by royal charters , the University of Edinburgh is constituted by the Universities (Scotland) Acts 1858 to 1966 . These acts provide for three major bodies in the governance of the university: the University Court , the General Council , and the Senatus Academicus . The University Court

12220-467: The plant genome by a T4SS mechanism. Cas9 and gRNA-based expression cassettes are turned into Ti plasmids , which are transformed in Agrobacterium for plant application. To improve Cas9 delivery in live plants, viruses are being used more effective transgene delivery. The ideal gene therapy practice is that which replaces the defective gene with a normal allele at its natural location. This

12350-538: The position since March 2011. Notable alumni of the University of Edinburgh include inventor Alexander Graham Bell , naturalist Charles Darwin , philosopher David Hume , physicist James Clerk Maxwell , and writers such as Sir J. M. Barrie , Sir Arthur Conan Doyle , Sir Walter Scott , and Robert Louis Stevenson . The university has produced several heads of state and government, including three British prime ministers . Additionally, three UK Supreme Court justices were educated at Edinburgh. As of October 2024,

12480-482: The possibilities include growth, disease resistance, sterility, controlled reproduction, and colour. Selecting for these traits can allow for a more sustainable environment and better welfare for the fish. AquAdvantage salmon is a genetically modified Atlantic salmon developed by AquaBounty Technologies. The growth hormone-regulating gene in the Atlantic salmon is replaced with the growth hormone-regulating gene from

12610-579: The possibility of unwanted homodimer activity and thus increase specificity of the DSB. Although the nuclease portions of both ZFNs and TALEN constructs have similar properties, the difference between these engineered nucleases is in their DNA recognition peptide. ZFNs rely on Cys2-His2 zinc fingers and TALEN constructs on TALEs. Both of these DNA recognizing peptide domains have the characteristic that they are naturally found in combinations in their proteins. Cys2-His2 Zinc fingers typically happen in repeats that are 3 bp apart and are found in diverse combinations in

12740-473: The proteins created for targeting each DNA sequence. Because off-target activity of an active nuclease would have potentially dangerous consequences at the genetic and organismal levels, the precision of meganucleases, ZFNs, CRISPR, and TALEN-based fusions has been an active area of research. While variable figures have been reported, ZFNs tend to have more cytotoxicity than TALEN methods or RNA-guided nucleases, while TALEN and RNA-guided approaches tend to have

12870-525: The public on 4 June 2024. Edinburgh has several historical links to other universities, chiefly through its influential Medical School and its graduates, who established and developed institutions elsewhere in the world. The university has five main sites in Edinburgh: The university is responsible for several significant historic and modern buildings across the city, including St Cecilia's Hall , Scotland's oldest purpose-built concert hall and

13000-448: The purported creation by Chinese scientist He Jiankui of the first gene-edited humans (see Lulu and Nana controversy ), the drafting of regulations that anyone manipulating the human genome by gene-editing techniques, like CRISPR , would be held responsible for any related adverse consequences. A cautionary perspective on the possible blind spots and risks of CRISPR and related biotechnologies has been recently discussed, focusing on

13130-475: The resulting NHEJ. ZFN was also used to drive herbicide-tolerance gene expression cassette (PAT) into the targeted endogenous locus IPK1 in this case. Such genome modification observed in the regenerated plants has been shown to be inheritable and was transmitted to the next generation. A potentially successful example of the application of genome editing techniques in crop improvement can be found in banana, where scientists used CRISPR/Cas9 editing to inactivate

13260-474: The rights of women to higher education on the national political agenda, which eventually resulted in legislation allowing women to study at all Scottish universities in 1889. The university admitted women to graduate in medicine in 1893. In 2015, the Edinburgh Seven were commemorated with a plaque at the university, and in 2019 they were posthumously awarded with medical degrees. Towards the end of

13390-448: The same term This disambiguation page lists articles associated with the same title formed as a letter–number combination. If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=BE3&oldid=1252922660 " Category : Letter–number combination disambiguation pages Hidden categories: Short description

13520-818: The school moved into a new £60 million building on the Easter Bush campus, which now houses research and teaching facilities, and a hospital for small and farm animals. Edinburgh College of Art , founded in 1760, formally merged with the university's School of Arts, Culture and Environment on 1 August 2011. In 2014, the Zhejiang University-University of Edinburgh Institute (ZJE) was founded as an international joint institute offering degrees in biomedical sciences, taught in English. The campus, located in Haining , Zhejiang Province, China,

13650-476: The second oldest in use in the British Isles ; Teviot Row House, the oldest purpose-built students' union building in the world; and the restored 17th-century Mylne's Court student residence at the head of the Royal Mile . The Central Area is spread around numerous squares and streets in Edinburgh's Southside , with some buildings in Old Town. It is the university's oldest area, occupied primarily by

13780-502: The sheep , the first mammal to be cloned from an adult cell. A year later Polly and Molly were cloned, both sheep contained a human gene. The Western General campus, in proximity to the Western General Hospital , contains the Biomedical Research Facility, Edinburgh Clinical Research Facility, and Institute of Genetics and Cancer (formerly the Institute of Genetics and Molecular Medicine). In common with

13910-526: The site for Moray House Institute for Education until it merged with the university on 1 August 1998. The university has since extended this campus. The buildings include redeveloped and extended Sports Science, Physical Education and Leisure Management facilities at St Leonard's Land linked to the Sports Institute in the Pleasance . The £80 million O'Shea Hall at Holyrood was named after

14040-528: The splicing function. Meganucleases method of gene editing is the least efficient of the methods mentioned above. Due to the nature of its DNA-binding element and the cleaving element, it is limited to recognizing one potential target every 1,000 nucleotides. ZFN was developed to overcome the limitations of meganuclease. The number of possible targets ZFN can recognized was increased to one in every 140 nucleotides. However, both methods are unpredictable because of their DNA-binding elements affecting each other. As

14170-457: The stochastic nature of cellular control processes. The University of Edinburgh Roslin Institute engineered pigs resistant to a virus that causes porcine reproductive and respiratory syndrome , which costs US and European pig farmers $ 2.6 billion annually. In February 2020, a US trial safely showed CRISPR gene editing on 3 cancer patients. In 2020 Sicilian Rouge High GABA, a tomato that makes more of an amino acid said to promote relaxation,

14300-456: The sum, the town council petitioned King James VI and his Privy Council . The King brokered a monetary compromise and granted a royal charter on 14 April 1582, empowering the town council to create a college of higher education. A college established by secular authorities was unprecedented in newly Presbyterian Scotland, as all previous Scottish universities had been founded through papal bulls . Named Tounis College (Town's College),

14430-484: The target site, thereby providing research and development tools that meet a wide range of needs (fundamental research, health, agriculture, industry, energy, etc.) These include the industrial-scale production of two meganucleases able to cleave the human XPC gene; mutations in this gene result in Xeroderma pigmentosum , a severe monogenic disorder that predisposes the patients to skin cancer and burns whenever their skin

14560-607: The teaching of rhetoric and poetry , alongside more traditional subjects such as philosophy . However, the bequest was delayed by more than 25 years due to the religious revolution that led to the Reformation Parliament of 1560. The plans were revived in the late 1570s through efforts by the Edinburgh Town Council , first minister of Edinburgh James Lawson , and Lord Provost William Little . When Reid's descendants were unwilling to pay out

14690-633: The time the Royal Society of Edinburgh was founded in 1783, the university was regarded as one of the world's preeminent scientific institutions, and Voltaire called Edinburgh a "hotbed of genius" as a result. Benjamin Franklin believed that the university possessed "a set of as truly great men, Professors of the Several Branches of Knowledge, as have ever appeared in any Age or Country". Thomas Jefferson felt that as far as science

14820-575: The university at the passing of the Act was vested in the Court. The present powers of the Court are further defined in the Universities (Scotland) Act 1966, including the administration and management of the university's revenue and property, the regulation of staff salaries, and the establishment and composition of committees of its own members or others. The General Council consists of graduates , academic staff , current and former University Court members. It

14950-453: The university has been affiliated with 20 Nobel Prize laureates, four Pulitzer Prize winners, three Turing Award winners, an Abel Prize laureate, and a Fields Medalist . Edinburgh alumni have also won a total of ten Olympic gold medals . In 1557, Bishop Robert Reid of St Magnus Cathedral on Orkney made a will containing an endowment of 8,000 merks to build a college in Edinburgh. Unusually for his time, Reid's vision included

15080-485: The university opened its doors to students on 14 October 1583, with an attendance of 80–90. At the time, the college mainly covered liberal arts and divinity . Instruction began under the charge of a graduate from the University of St Andrews , theologian Robert Rollock , who first served as Regent, and from 1586 as principal of the college. Initially Rollock was the sole instructor for first-year students, and he

15210-465: The university, alongside the Royal Infirmary of Edinburgh. The campus houses the Anne Rowling Regenerative Neurology Clinic, Centre for Regenerative Medicine , Chancellor's Building, Euan MacDonald Centre , and Queen's Medical Research Institute, which opened in 2005. The Chancellor's Building has two large lecture theatres and a medical library connected to the Royal Infirmary of Edinburgh by

15340-413: The university, and to receive an audited financial statement . The Council elects the chancellor of the university and three Assessors on the University Court. The Senatus Academicus is the university's supreme academic body, chaired by the principal and consisting of the professors, heads of departments, and a number of readers , lecturers and other teaching and research staff. The core function of

15470-582: Was approved for sale in Japan. In 2021, England (not the rest of the UK) planned to remove restrictions on gene-edited plants and animals, moving from European Union -compliant regulation to rules closer to those of the US and some other countries. An April 2021 European Commission report found "strong indications" that the current regulatory regime was not appropriate for gene editing. Later in 2021, researchers announced

15600-609: Was concerned, "no place in the world can pretend to a competition with Edinburgh". In 1785, Henry Dundas introduced the South Bridge Act in the House of Commons ; one of the bill's goals was to use South Bridge as a location for the university, which had existed in a hotchpotch of buildings since its establishment. The site was used to construct Old College , the university's first custom-built building, by architect William Henry Playfair to plans by Robert Adam . During

15730-560: Was established on 15 March 2016. The university began hosting a Wikimedian in Residence in 2016. The residency was made into a full-time position in 2019, with the Wikimedian involved in teaching and learning activities within the scope of the University of Edinburgh WikiProject . In 2018, the University of Edinburgh was a signatory to the £1.3 billion Edinburgh and South East Scotland City Region Deal , in partnership with

15860-461: Was established to ensure that graduates have a continuing voice in the management of the university. The Council is required to meet twice per year to consider matters affecting the wellbeing and prosperity of the university. The Universities (Scotland) Act 1966 gave the Council the power to consider draft ordinances and resolutions, to be presented with an annual report of the work and activities of

15990-420: Was expected to tutor the 1583 intake for all four years of their degree in every subject. The first cohort finished their studies in 1587, and 47 students graduated (or 'laureated') with an M.A. degree. When King James VI visited Scotland in 1617, he held a disputation with the college's professors, after which he decreed that it should henceforth be called the "Colledge [sic] of King James". The university

16120-460: Was found, its cleaving portion could be separated which would be very non-specific as it would have no recognition ability. This portion could then be linked to sequence recognizing peptides that could lead to very high specificity. Zinc finger motifs occur in several transcription factors . The zinc ion, found in 8% of all human proteins, plays an important role in the organization of their three-dimensional structure. In transcription factors, it

16250-682: Was founded in 1884 by student Robert Fitzroy Bell . In 1889, the SRC voted to establish Edinburgh University Union (EUU), to be housed in Teviot Row House on Bristo Square. Edinburgh University Sports Union (EUSU) was founded in 1866, and Edinburgh University Women's Union (renamed the Chambers Street Union in 1964) in October 1905. The SRC, EUU and Chambers Street Union merged to form Edinburgh University Students' Association (EUSA) on 1 July 1973. During World War I ,

16380-684: Was in the treatment of CD19+ acute lymphoblastic leukemia in an 11-month old child in 2015. Modified donor T cells were engineered to attack the leukemia cells, to be resistant to Alemtuzumab , and to evade detection by the host immune system after introduction. Extensive research has been done in cells and animals using CRISPR-Cas9 to attempt to correct genetic mutations which cause genetic diseases such as Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes. In February 2019, medical scientists working with Sangamo Therapeutics , headquartered in Richmond, California , announced

16510-606: Was known as both Tounis College and King James' College until it gradually assumed the name of the University of Edinburgh during the 17th century. After the deposition of King James II and VII during the Glorious Revolution in 1688, the Parliament of Scotland passed legislation designed to root out Jacobite sympathisers amongst university staff. In Edinburgh, this led to the dismissal of Principal Alexander Monro and several professors and regents after

16640-598: Was originally intended for students and doctors in the Polish Armed Forces in the West , civilians were also allowed to take the courses, which were taught in Polish and awarded Polish medical degrees. When the school was closed in 1949, 336 students had matriculated, of which 227 students graduated with the equivalent of an MBChB and a total of 19 doctors obtained a doctorate or MD. A bronze plaque commemorating

16770-687: Was renamed the Moray House School of Education and Sport in August 2019. In the 1990s it became apparent that the old Royal Infirmary of Edinburgh buildings in Lauriston Place were no longer adequate for a modern teaching hospital. Donald Dewar , the Scottish Secretary at the time, authorized a joint project between private finance, local authorities, and the university to create a modern hospital and medical campus in

16900-411: Was seen as too ambitious. The new Medical School opened in 1884, but the building was not completed until 1888. After funds were donated by politician and brewer William McEwan in 1894, a separate graduation building was constructed after all, also designed by Anderson. The resulting McEwan Hall on Bristo Square was presented to the university in 1897. The Students' Representative Council (SRC)

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