Monday, December 21, 2020
Virus VUI – 202012/01 - B117
Virus VUI – 202012/01 - B117
A new variant of the virus that causes COVID-19 (SARS-CoV-2) has been identified across the South East of England. The variant has been named ‘VUI – 202012/01’ (the first Variant Under Investigation in December 2020).
This variant includes a mutation in the ‘spike’ protein. The new highly transmissible strain has shown a similar lethal effect as other variant strains but it contains key mutations, particularly in the virus receptor domain.
A virus is a small parasite that cannot reproduce by itself. Once it infects a susceptible cell, however, a virus can direct the cell machinery to produce more viruses. Most viruses have either RNA or DNA as their genetic material. The nucleic acid may be single- or double-stranded. The entire infectious virus particle, called a virion, consists of the nucleic acid and an outer shell of protein. The simplest viruses contain only enough RNA or DNA to encode four proteins. The most complex can encode 100 – 200 proteins.
Strictly speaking, viruses can't die, for the simple reason that they aren't alive in the first place. Although they contain genetic instructions in the form of DNA (or the related molecule, RNA), viruses can't thrive independently. Instead, they must invade a host organism and hijack its genetic instructions.
Antibodies are proteins that recognise and bind parts of viruses to neutralise them. Antibodies are produced by our white blood cells and are a major part of the body's response to combatting a viral infection. Antigens are substances that cause the body to produce antibodies, such as a viral protein.
For most viral infections, treatments can only help with symptoms while you wait for your immune system to fight off the virus. Antibiotics do not work for viral infections. There are antiviral medicines to treat some viral infections. Vaccines can help prevent you from getting many viral diseases.
Monday, August 19, 2013
The Synthetic Cell
The Synthetic Cell
In 2010 the James Craig Venter Institute in the US successfully created a synthetic cell. What this means is they made a genome for a cell synthetically and then injected that into a host cell, which then accepted this new DNA and continued to function and replicate as a normal cell would. This discovery could lead to improvements in many different industries around the world.
Despite sounding very simple in theory this process was actually very hard for James Venter and his team to complete. It took them 15 years in total to work through how to complete each step of the process before finally combining all of their knowledge to finally create the cell. The whole experiment is explained in length here http://www.sciencemag.org/content/329/5987/52.full. The cell that was used was no animal or anything complex like that, the cell they chose was yeast. This may seem a little odd as yeast isn’t particularly interesting but Venter’s team chose this cell due to its small genome size. After all this experiment was only a proof of concept and they were only trying to show that a synthetic cell could be made not what could be done with one.
Because of this amazing breakthrough many advancements will appear very soon in other fields. The James Craig Venter Institute has already stuck a deal with oil company Exxon Mobil to produce algae synthetically to create biofuels. This will have a huge impact upon the oil industry if there is an alternative energy source available. Another improvement that can result is a complete new process to administer vaccines. Instead of getting vaccines through a needle it could be possible to synthetically create the cells and put them inside of a pill that could be swallowed. This would make taking vaccinations much less invasive. But the institute isn’t too worried about these new advancements. They are now turning their attention to improving our understanding of what creates life inside of a cell. To do this they are going to determine which parts of DNA a cell can’t survive without and then from this they will know the absolute minimum requirements for life inside of a cell. This will change the field of genetics immensely as there is still a large amount that is unknown. This further research with the aid of synthetically altered cells could help scientists to understand exactly what each gene does inside of a cell.
This might all sound like something taken straight from a movie but I assure you this is real and is happening now. In the very near future many fields will be affected by the creation of this synthetic cell and we will be the ones who will be able to reap the rewards. This is only scratching the surface of what science will be capable of in coming years.
In 2010 the James Craig Venter Institute in the US successfully created a synthetic cell. What this means is they made a genome for a cell synthetically and then injected that into a host cell, which then accepted this new DNA and continued to function and replicate as a normal cell would. This discovery could lead to improvements in many different industries around the world.
Despite sounding very simple in theory this process was actually very hard for James Venter and his team to complete. It took them 15 years in total to work through how to complete each step of the process before finally combining all of their knowledge to finally create the cell. The whole experiment is explained in length here http://www.sciencemag.org/content/329/5987/52.full. The cell that was used was no animal or anything complex like that, the cell they chose was yeast. This may seem a little odd as yeast isn’t particularly interesting but Venter’s team chose this cell due to its small genome size. After all this experiment was only a proof of concept and they were only trying to show that a synthetic cell could be made not what could be done with one.
Because of this amazing breakthrough many advancements will appear very soon in other fields. The James Craig Venter Institute has already stuck a deal with oil company Exxon Mobil to produce algae synthetically to create biofuels. This will have a huge impact upon the oil industry if there is an alternative energy source available. Another improvement that can result is a complete new process to administer vaccines. Instead of getting vaccines through a needle it could be possible to synthetically create the cells and put them inside of a pill that could be swallowed. This would make taking vaccinations much less invasive. But the institute isn’t too worried about these new advancements. They are now turning their attention to improving our understanding of what creates life inside of a cell. To do this they are going to determine which parts of DNA a cell can’t survive without and then from this they will know the absolute minimum requirements for life inside of a cell. This will change the field of genetics immensely as there is still a large amount that is unknown. This further research with the aid of synthetically altered cells could help scientists to understand exactly what each gene does inside of a cell.
This might all sound like something taken straight from a movie but I assure you this is real and is happening now. In the very near future many fields will be affected by the creation of this synthetic cell and we will be the ones who will be able to reap the rewards. This is only scratching the surface of what science will be capable of in coming years.
RNA-only genes: ancient infections hide in human genome and get themselves passed from generation to generation
RNA-only genes: ancient infections hide in human genome and get themselves passed from generation to generation
From the Economist:
Not so long ago, received wisdom was that most of the human genome—99% of it—was “junk”. If this junk had a role, it was just to space out the remaining 1%, the genes in which instructions about how to make proteins are encoded.
That, it now seems, was far from the truth. The decade since the completion of the Human Genome Project has shown that lots of the junk must indeed have a function. Almost two-thirds of human DNA, rather than just 1% of it, is being copied into molecules of RNA. As a consequence, rather than there being just 23,000 genes, there may be millions of them.
Human chromosomes (grey) capped by telomeres (white). Image source: Wikipedia, public domain.
One new genetic class is known as lincRNAs. Molecules of lincRNA are similar to the messenger-RNA molecules which carry protein blueprints. However, they do not encode proteins. More than 9,000 sorts are known, and their job is the regulation of other genes.
LincRNA is rather odd, though. It often contains members of a second class of weird genetic object. These are called transposable elements - “jumping genes” - because their DNA can hop from one place to another within the genome. Transposable elements come in several varieties, but one group of particular interest are known as endogenous retroviruses. These are the descendants of ancient infections that have managed to hide away in the genome and get themselves passed from generation to generation along with the rest of the genes.
From the Economist:
Not so long ago, received wisdom was that most of the human genome—99% of it—was “junk”. If this junk had a role, it was just to space out the remaining 1%, the genes in which instructions about how to make proteins are encoded.
That, it now seems, was far from the truth. The decade since the completion of the Human Genome Project has shown that lots of the junk must indeed have a function. Almost two-thirds of human DNA, rather than just 1% of it, is being copied into molecules of RNA. As a consequence, rather than there being just 23,000 genes, there may be millions of them.
Human chromosomes (grey) capped by telomeres (white). Image source: Wikipedia, public domain.
One new genetic class is known as lincRNAs. Molecules of lincRNA are similar to the messenger-RNA molecules which carry protein blueprints. However, they do not encode proteins. More than 9,000 sorts are known, and their job is the regulation of other genes.
LincRNA is rather odd, though. It often contains members of a second class of weird genetic object. These are called transposable elements - “jumping genes” - because their DNA can hop from one place to another within the genome. Transposable elements come in several varieties, but one group of particular interest are known as endogenous retroviruses. These are the descendants of ancient infections that have managed to hide away in the genome and get themselves passed from generation to generation along with the rest of the genes.
RNAi: Curing Genetic Disease
RNAi: Curing Genetic Disease
Destined from conception, sufferers of genetic diseases have very poor prospects of finding cures, with most medical treatments only mitigating or slowing symptom progression, condemning them to a curtailed lifespan and reduced quality of life. With the advancement of RNA interference research, a world of possibilities may be uncovered for treatments of genetic disorders that offer effective, long-term solutions.
Autosomal disorders are nearly impossible to cure as the patient’s DNA is the origin of the disease. Both traditional and RNAi treatments attempt to manipulate gene activity or influence gene products such as protein synthesis. However, current pharmacological therapies for genetic disorders have several notable shortcomings, namely the delivery of drugs, targeting and specificity (Seyhan, 2011). Conventional drugs are commonly unable to access and target clinically relevant particles, creating so-called “undruggable” targets. Furthermore, current methodologies lack specificity, frequently unable to act upon target gene sequences without affecting other chemically similar sequences, resulting in undesired, uncontrolled “off-targeting” (Seyhan, 2011). In comparison, RNAi can theoretically be used to silence any gene with pinpoint accuracy, which greatly expands the potential reach of medicine (National Institute of General Medical Sciences, 2012).
Figure 1. Double-stranded RNA (ScienceLibraryPhoto)
Silencing of genes is in essence, sabotaging the process of protein synthesis. Specially modified viral or plasmids vectors are used to introduce double stranded RNA into target cells. Once taken into the host nucleus, the dsRNA undergoes a complex progression of chemical changes. Firstly, RNase III enzymes called Drosha cleave the introduced dsRNA into strands of 60-70 nucleotides known as precursor-microRNA or small hairpin RNA. After being transported from the nucleus to the cytoplasm, another RNase III enzyme called Dicer cleaves the precursor-microRNA to form small interfering RNA, which are 19-25 nucleotides long. The small interfering RNA binds with a protein complex named RISC, and directs the degradation of the complementary mRNA sequence produced by the host cell’s DNA. This is the crucial step which gives RNA interference one of its main advantages over conventional therapies, specificity, as RISC will only activate and destroy mRNA which matches the small interfering RNA bound to it. Degraded mRNA means the defective sequence is not translated and so the mutant protein will not be produced (Seyhan, 2011).
Figure 2. RNA interference process (Seyhan, 2011)
Theoretically, RNAi can alleviate any disorder caused or impacted by proteins, covering a wide range of diseases including HIV, Hepatitus C and Huntington’s Disease. Notably with Huntington’s where defective genes produce toxic proteins especially damaging to motor neurons, there has already been several successful trials on rodents (National Institute of General Medical Sciences, 2012). By silencing the Huntingtin gene in mice, levels of mutant Htt proteins were reduced with notable improvements in motor function, although challenges remain in improving potency and specificity.
Figure 3. Motor function test on Rotarod (National Phenotyping Center)
Researchers have just started to uncover the potential behind this science and there have been successes with ongoing studies; however, the classic challenges in treating genetic disorders such as drug delivery, targeting and specificity are hampering the development of effective RNAi treatments. Despite this, current scientific understandings show RNAi to be a vast and promising avenue of progress.
Bibliography
National Institute of General Medical Sciences, 2012. RNA Interference Fact Sheet. [Online] Available at: http://www.nigms.nih.gov/News/Extras/RNAi/factsheet.html [Accessed 17 March 2012].
National Phenotyping Center, 2008. Rota-rod Test. [Online] Available at: http://tmc.sinica.edu.tw/rotarod.html [Accessed 17 March 2012].
ScienceLibraryPhoto, n.d. Double-stranded RNA molecule. [Online] Available at: http://www.sciencephoto.com/media/210478/enlarge [Accessed 17 March 2012].
Seyhan, A. A., 2011. RNAi: a potential new class of therapeutic for human genetic disease. Human Genetics, 130(5), pp. 583-605.
Wasi, S., 2003. RNA interference: the next genetics revolution?. [Online] Available at: http://www.nature.com/horizon/rna/background/interference.html [Accessed 17 March 2012].
Destined from conception, sufferers of genetic diseases have very poor prospects of finding cures, with most medical treatments only mitigating or slowing symptom progression, condemning them to a curtailed lifespan and reduced quality of life. With the advancement of RNA interference research, a world of possibilities may be uncovered for treatments of genetic disorders that offer effective, long-term solutions.
Autosomal disorders are nearly impossible to cure as the patient’s DNA is the origin of the disease. Both traditional and RNAi treatments attempt to manipulate gene activity or influence gene products such as protein synthesis. However, current pharmacological therapies for genetic disorders have several notable shortcomings, namely the delivery of drugs, targeting and specificity (Seyhan, 2011). Conventional drugs are commonly unable to access and target clinically relevant particles, creating so-called “undruggable” targets. Furthermore, current methodologies lack specificity, frequently unable to act upon target gene sequences without affecting other chemically similar sequences, resulting in undesired, uncontrolled “off-targeting” (Seyhan, 2011). In comparison, RNAi can theoretically be used to silence any gene with pinpoint accuracy, which greatly expands the potential reach of medicine (National Institute of General Medical Sciences, 2012).
Figure 1. Double-stranded RNA (ScienceLibraryPhoto)
Silencing of genes is in essence, sabotaging the process of protein synthesis. Specially modified viral or plasmids vectors are used to introduce double stranded RNA into target cells. Once taken into the host nucleus, the dsRNA undergoes a complex progression of chemical changes. Firstly, RNase III enzymes called Drosha cleave the introduced dsRNA into strands of 60-70 nucleotides known as precursor-microRNA or small hairpin RNA. After being transported from the nucleus to the cytoplasm, another RNase III enzyme called Dicer cleaves the precursor-microRNA to form small interfering RNA, which are 19-25 nucleotides long. The small interfering RNA binds with a protein complex named RISC, and directs the degradation of the complementary mRNA sequence produced by the host cell’s DNA. This is the crucial step which gives RNA interference one of its main advantages over conventional therapies, specificity, as RISC will only activate and destroy mRNA which matches the small interfering RNA bound to it. Degraded mRNA means the defective sequence is not translated and so the mutant protein will not be produced (Seyhan, 2011).
Figure 2. RNA interference process (Seyhan, 2011)
Theoretically, RNAi can alleviate any disorder caused or impacted by proteins, covering a wide range of diseases including HIV, Hepatitus C and Huntington’s Disease. Notably with Huntington’s where defective genes produce toxic proteins especially damaging to motor neurons, there has already been several successful trials on rodents (National Institute of General Medical Sciences, 2012). By silencing the Huntingtin gene in mice, levels of mutant Htt proteins were reduced with notable improvements in motor function, although challenges remain in improving potency and specificity.
Figure 3. Motor function test on Rotarod (National Phenotyping Center)
Researchers have just started to uncover the potential behind this science and there have been successes with ongoing studies; however, the classic challenges in treating genetic disorders such as drug delivery, targeting and specificity are hampering the development of effective RNAi treatments. Despite this, current scientific understandings show RNAi to be a vast and promising avenue of progress.
Bibliography
National Institute of General Medical Sciences, 2012. RNA Interference Fact Sheet. [Online] Available at: http://www.nigms.nih.gov/News/Extras/RNAi/factsheet.html [Accessed 17 March 2012].
National Phenotyping Center, 2008. Rota-rod Test. [Online] Available at: http://tmc.sinica.edu.tw/rotarod.html [Accessed 17 March 2012].
ScienceLibraryPhoto, n.d. Double-stranded RNA molecule. [Online] Available at: http://www.sciencephoto.com/media/210478/enlarge [Accessed 17 March 2012].
Seyhan, A. A., 2011. RNAi: a potential new class of therapeutic for human genetic disease. Human Genetics, 130(5), pp. 583-605.
Wasi, S., 2003. RNA interference: the next genetics revolution?. [Online] Available at: http://www.nature.com/horizon/rna/background/interference.html [Accessed 17 March 2012].
Genetics and Obesity
Genetics and Obesity
Obesity, classified as a chronic disease by the World Health Organization (WHO) is regarded as having irregular or excessive fat accumulation. It can be measured and quantified by examining ones body mass index (BMI), where on average, anyone over 30kg/m2 would be classified as obese (WHO 2012). Obesity is followed by a large number of health risks (including diabetes, cardiovascular diseases, cancer and more) and generally decreases life expectancy. What has been discovered recently is that genetics plays a large role in obesity, specifically the role of melanocortin 4 receptors (MC4R) and how dysfunction of the receptors can lead to an onset of obesity (Logan MG et al. 2010).
Although obesity is commonly known to be caused by the imbalance in calorie consumption and energy output, recent research has illustrated the genetic factor that can be taken into account for certain individuals, therefore making obesity a multi-factorial disease. MC4R has largely been known to maintain energy homeostasis by regulating the body’s food intake. It does so by providing an anorexigenic signal, which is a result of the binding of an agonist (alpha-melanocyte-stimulating hormone) to the receptor, allowing one to have the sensation of being full (Logan MG et al. 2010). Due to the multiple mutations that MC4R is susceptible to some individuals will be more likely to become obese than others with the pathogenic MC4R. MC4R polymorphisms do not actually impair an individual’s rate of energy expenditure, but rather affects their appetite causing a hyperphagic state. Phenotypes that usually follow this kind of mutation include increase in fat or growth, eating disorders (binge-eating) and hyperinsulinaemia (abnormally high levels of insulin circulation). The reason that MC4R polymorphisms result in such phenotypes is largely due to the hindered functionality of the MC4 receptor (Logan MG et al. 2010). Mutated MC4R is observed to have decreased or absent ligand binding, decreased cell surface receptor expression, incorrect protein formation, and reduced signal transduction. Of these defects, those that interfere with intracellular reception (compromises the functionality and activity of the receptors) are linked to more severe forms of obesity. This allows fairly accurate predictions to be made about the onset and severity of obesity in people with pathogenic MC4R mutations. More importantly, carriers of pathogenic MC4R have an 82% chance of passing it onto their offspring, increasing the odds of being obese by almost 5 times (note that ethnicity is also a variable) (Logan MG et al. 2010). Lastly, the polymorphism or mutation that can be identified in the MC4R gene does not imply that either the mutation is involved in the pathogenesis of the disease and that the subject will have the observed phenotypes.
There are simply too many factors that can come into account when attempting to overcome such an epidemic as obesity; however by understanding how genetics affects obesity treatments can be enhanced and diversified to create more effective treatments for patient. By being able to predict such abnormalities through the mutations of MC4R, obesity can be prevented before onset. Theorized treatments aim to suppress appetite by increasing neural sensitivity to insulin and leptin; however current research has yet to bring forth concrete solutions to this disease (Christian N 2012).
Obesity, classified as a chronic disease by the World Health Organization (WHO) is regarded as having irregular or excessive fat accumulation. It can be measured and quantified by examining ones body mass index (BMI), where on average, anyone over 30kg/m2 would be classified as obese (WHO 2012). Obesity is followed by a large number of health risks (including diabetes, cardiovascular diseases, cancer and more) and generally decreases life expectancy. What has been discovered recently is that genetics plays a large role in obesity, specifically the role of melanocortin 4 receptors (MC4R) and how dysfunction of the receptors can lead to an onset of obesity (Logan MG et al. 2010).
Although obesity is commonly known to be caused by the imbalance in calorie consumption and energy output, recent research has illustrated the genetic factor that can be taken into account for certain individuals, therefore making obesity a multi-factorial disease. MC4R has largely been known to maintain energy homeostasis by regulating the body’s food intake. It does so by providing an anorexigenic signal, which is a result of the binding of an agonist (alpha-melanocyte-stimulating hormone) to the receptor, allowing one to have the sensation of being full (Logan MG et al. 2010). Due to the multiple mutations that MC4R is susceptible to some individuals will be more likely to become obese than others with the pathogenic MC4R. MC4R polymorphisms do not actually impair an individual’s rate of energy expenditure, but rather affects their appetite causing a hyperphagic state. Phenotypes that usually follow this kind of mutation include increase in fat or growth, eating disorders (binge-eating) and hyperinsulinaemia (abnormally high levels of insulin circulation). The reason that MC4R polymorphisms result in such phenotypes is largely due to the hindered functionality of the MC4 receptor (Logan MG et al. 2010). Mutated MC4R is observed to have decreased or absent ligand binding, decreased cell surface receptor expression, incorrect protein formation, and reduced signal transduction. Of these defects, those that interfere with intracellular reception (compromises the functionality and activity of the receptors) are linked to more severe forms of obesity. This allows fairly accurate predictions to be made about the onset and severity of obesity in people with pathogenic MC4R mutations. More importantly, carriers of pathogenic MC4R have an 82% chance of passing it onto their offspring, increasing the odds of being obese by almost 5 times (note that ethnicity is also a variable) (Logan MG et al. 2010). Lastly, the polymorphism or mutation that can be identified in the MC4R gene does not imply that either the mutation is involved in the pathogenesis of the disease and that the subject will have the observed phenotypes.
There are simply too many factors that can come into account when attempting to overcome such an epidemic as obesity; however by understanding how genetics affects obesity treatments can be enhanced and diversified to create more effective treatments for patient. By being able to predict such abnormalities through the mutations of MC4R, obesity can be prevented before onset. Theorized treatments aim to suppress appetite by increasing neural sensitivity to insulin and leptin; however current research has yet to bring forth concrete solutions to this disease (Christian N 2012).
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