Tuesday, 28 August 2012

Recruiting AIDS to Combat Cancer


Recruiting AIDS to Combat Cancer


Using the AIDS Virus to fight Cancer? Yes, that’s right; as this may appear as a strange medical endevor to get your head around, recent genetic research conducted by a CRNS team at the RNA Architecture and Reactivity laboratory has found a certain mutant protein in HIV that posses incredible replication properties which can be used with aniticancer drugs to fight cancer. The uniqueness of this newly developed treatment is said to be able to treat patents with toxic drug doses up to 300 times lower than without the addition of the HIV virus.



The human immunodeficiency virus (HIV-1), which causes AIDS, uses human cells to replicate itself by inserting its genetic information into the host cell. What has scientists interested is that HIV mutates constantly and spreads from cell to cell at a fast rate. This enables the virus to adapt to avoid many treatments that are used against the virus today.



Although, why would anyone want to risk contracting the HIV virus when they are receiving treatment for a cancer tumour? This is not apparent; effects of the retrovirus are rechanneled for therapeutic applications, indeed the treatment of cancer. Scientists have improved the HIV genome by adding a gene for deoxycytidine kinase (dCK), which is a human protein that’s involved in the activation of drugs inside cells (PLoS Genetics, 2012). Through the manipulation of the HIV genome, the CNRS team has ran tests of over 80 mutant proteins and tested them with anticancer drugs on tumour cells. Out of the 80 proteins tested the team found a deoxycytidine kinase variant that is more effective than a protein in which isn’t mutated. This protein showed great effectiveness in inducing death to cancer cells (PLoS Genetics, 2012).

CNRS scientists have labelled this process as ‘The Retrovolution system’. In this system the replication genetics of HIV-1 are utilised to run the evolution of cellular genes. This continuously occurs by successive infection cycles with HIV-1 viral vectors, which are a tool that molecular biologists use to deliver genetic material into target cells. These viral vectors contain a target sequence of the evolved genetic material inserted into their RNA.  Therefore French scientists wanted to mutate many variants of the deoxycytidine kinase (dCK) gene; while isolating an enzyme that was able to increase the sensitivity to therapeutic drugs, such as anticancer compounds known as deoxycytidine analogues (PLoS Genetics, 2012). In a simpler form, after the HIV ridden drugs ‘enters the target cell, the viral polymerase converts the viral genomic RNA, throughout an error-prone process that generates genetic diversity, into double-stranded DNA, which is then integrated in the genome of the cell’ (PLoS Genetics, 2012).


Many studies still need to be conducted with this genetic discovery before it can be passed as a viable cancer treatment since some properties of the deoxycytidine kinase aren’t predictable on a rational basis. However, reducing patent doeses of anticancer medicines would provide great help in the overall effectiveness of the treatment, since these drugs produce negative side effects. Thus, using a deadly virus for therapeutic treatment is likely to lead into great medical advances in the future.

                                    References 

Paola Rossolillo, Flore Winter, Etienne Simon-Loriere, Sarah Gallois-Montbrun, Matteo Negroni. Retrovolution: HIV–Driven Evolution of Cellular Genes and Improvement of Anticancer Drug Activation. PLoS Genetics, 2012; 8 (8): e1002904 DOI:

http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002904?imageURI=info:doi/10.1371/journal.pgen.1002904.g001

HIV picture: http://24.media.tumblr.com/tumblr_lsh0rbzaUV1qc6n7jo1_500.png
Lab Picture : http://www.medgenetics.ru/english/Laboratories/Evolutionary_Genetics/

Saturday, 25 August 2012

Using Genetic Information to Evaluate and Ultimately Take Action to Preserve the Himalayan Snowcock


Using Genetic Information to Evaluate and Ultimately Take Action to Preserve the Himalayan Snowcock (Tetaogallus himalayensis)
The human race has had to face many harsh realities recently such as climate change and animal extinction due to our ignorance of the delicate systems working together to create our biosphere. Scientists are using recent genetic technology to gain a better understanding of our biosphere so we can nurture and take action to repair it. Researchers of Nanchang University in China investigated the relationship between the degree of genetic variation in the Himalayan Snowcock (Tetaogallus himalayensis) and the environment. The environment has differing effects of genetic diversity depending on the species, with little similarity between different bird species concerning these differences (Ruan et al, 2012).
The Snowcock (Tetaogallus himalayensis) is a sedentary ground bird which resides in the Himalayas. They prefer to escape the warmer weather in summer into the high mountains. During the winter, however, they inhabit the lower foothills of the mountains including fluvial rocky hills, alpine meadows, hilly pastures and barren shrubby grassland (Cheng 1978) where it is warmer. Ultimately they prefer cool weather and minimal physical activity (Ruan et al, 2012). http://www.kolkatabirds.com/himalayansnowcock8dm.jpg
For a population to survive, the genetic diversity needs be able to survive natural selection regarding changes in the environment. This diversity is quantitatively obvious to scientists through Single Nucleotide Morphism (SNPs) which occur in the in the DNA sequence in the form of varying nucleotide sequence lengths and sites as well as pairwise differences. Singularly or collectively these SNPs may results in an expressed difference known as a polymorph. This may include changes in colours, resistances, etc in a particular unit or offspring. These polymorphic sites are grouped by their effective change and are called haplotypes (Reece et al, 2012). Many haplotypes are desirable to increase the strength and resistance of a population to changes in the environment. This is considerably important since the environment is changing due to the human’s effects; so diversity in the genome of the Snowcock (Tetaogallus himalayensis) is essential to its survival.
Biologists tried to determine the best environment to encourage genetic diversity in the Snowcock (Tetaogallus himalayensis). Since the degree of how much variability relies on the environment varies among bird species (Raun et al, 2012) it can’t be prescribed and each species must be researched individually. Upon testing groups of the same species which resided in different areas of the same region, they soon discovered the degree of genetic diversity was strongly related to how many hours of sunlight habitat was exposed to. The more sunlight there was the number of unique haplotypes was less which means less variability in the population. In these places the population is at an increased risk of extinction. Their explanation referred to another study which suggested that sunshine duration and intensity could affect sex gland development. The researches recommended a shorter annual sunshine duration and more sunshine duration variation to improve genetic diversity.
Our understanding of the environment inclusive of its fauna is essential to the survival of humans and the health of our planet. Through carrying out this research scientists are adding to the pool of collective knowledge which can be understood and adapted by another for another application.


Bibliography


Reece, J., Meyers, N., Urry , L., Cain, M., Wasserman, S., Jackson, R., et al. (2012). Campbell Biology (9 ed.). Melbourne: Pearson.
Ruan, L., Luo, H., Zhang, L., & Wen, L. (2012). Ecological Genetics of Himalayan Snowcock (Tetaogallus himalayensis). Berlin: SpringerLink.



Thursday, 23 August 2012

Evolutionary Development by Rob Urquhart


By Rob Urquhart
Evolution is the change in the gene pool of a population over time . A population may evolve when individuals differ in one or more heritable traits that are responsible for differences in the ability to survive and reproduce. The individuals with traits that enable them to out compete their competition are more likely to survive and pass their genes onto the next generation these traits are called adaptations.
 An adaptation is any genetically controlled feature or ability which increases an organism’s chance of survival and therefore its ability to pass on its genes. However an adaptation is only adaptive in present time and location.
Moving from water to land took generations and generations of slight adaptations. The competition for area, food and mates are believed to of driven the advance of the evolution from water to land.
If I was to ask you which evolved from what; the dog to the whale or the whale to the dog, I'd suggest the vast majority would get it wrong. About 300 million years after fish first made it to land, the land dwellers moved back. A discovery made shows that a bone in the hip from a wolf is the same type as a bone found in a whale. At first everyone thought it was from whale to wolf but the first aquatic animals all had vertical tail fins and did not have this bone.
The evolution of the Equus or commonly known as the horse took about 55million years. Through fossils we can essentially see the evolution taking place. The main characteristic change is the loss of the number of digits. The original 'dawn horse' had four digits which it ran on, however over time three digits slowly receded until they became nonexistent. This loss of the digits enabled the horse to move quicker with less energy.
Mutations are the variation of the alleles of a specific gene. These may spread (assuming the gene still works efficiently) throughout the population and thus cause a variation in the gene pool. If this mutation aids in the survival of the individuals (an adaptation) then it can in a number of generations cause the population to evolve.
Mutated alleles may be recessive or dominant, recessive means that the gene is only expressed in the absence of the dominant. But these mutated alleles may not necessarily be an adaptation for example polydactyl. Polydactyl was a mutation in the founders of the Amish community. It commonly occurs due to inbreeding. When inbreeding occurs the offspring will not have a wide enough gene pool so mutations like polydactyl can occur as the offspring may get two recessive alleles for the trait.
British Royal Family known for interbreeding as to keep their blood 'pure'. This allowed the disease haemophilia to be passed through the offspring.



Nicholas Dwyer Archaeogenetics Blog


A Mammoth Discovery
By Nicholas Dwyer

Archaeogenetics was a term first brought about by “Colin Renfrew” which has been now defined into three areas, these are; the analysis of ancient DNA, the analysis of DNA from past generations of human societies (plant and human material) and the application of statistical methods developed by molecular geneticists to archaeological data. The growth of the genetics field which has come with the major advancements of technology within the field has helped promote this new area and possesses the ability to answer many questions of the past.

As technology has improved exponentially within the last twenty years within the field of genetics it has opened the possibility of the recreation of extinct organisms, perhaps even organisms such as the Mammoth. For organisms that have been extinct for thousands or millions of years there are problems with finding material that may possess genetic material and even if they do possess some genetic material it is highly degraded. While there is little hope that any dinosaurs will be found with enough genetic material that can be salvaged there is some hope in regards to mammoths with a number of specimens found intact with organs and skin intact. In order to produce a mammoth they could perform two methods depending on what genetic material is found. The recent discovery of Jarkov a male 47 year old mammoth who was in relatively good condition is where they hope to obtain the material. If Jarkov has sperm cells that are in a retrievable condition then it may be possible to artificially inseminate a female Asiatic elephant egg. A past mammoth specimen was found to be closely related to the Asiatic elephant. If there are no recoverable sperm cells then it may be possible to use the same method of cloning used for Dolly the sheep. This would require a healthy somatic cell for the somatic cell nuclear transfer method. Many seem skeptical that this is within the realms of possibility as the cells could not possibly survive in permafrost  and these methods require living cells.
Though cloning is when of the first things that comes with the discovery of ancient DNA it also may help increase our understanding of the mammoth. As Jarkov is a complete specimen he may contain evidence of what could have possibly caused the Mammoths to go extinct which some scientists have hypothesized may be related to a disease or virus. With its DNA they may be able to identify its similarities with the two existing elephants and possibly determine where they diverged genetically. The knowledge that can be obtained from specimens like this is critical in helping build the field of archaeogenetics and may help in awareness of the area as well as show where future improvements can be made in obtaining information from the specimen.

Though archaeogenetics has yet to make a sgnificant impact on the scientific community it is an area of great potential and will surely become more prominent as technology increases and more materials are discovered.

Plants Cloned as Seeds: A Step Towards Artificial Apomixis



Once upon a time, plant breeders have envisioned the potential of apomixis but it still seemed to be so far away. Recent findings in agricultural science, however, showed that it is starting to come within our reach. As said by Simon Chan, assistant professor of plant biology at UC Davis, “plants have for the first time been cloned as seeds... a major step towards making hybrid crop plants that can retain favorable traits from generation to generation”.

Plants such as dandelions and hawkeed can produce seeds that are exact genetic replicas of their parent without having to go through recombination that occurs during sexual reproduction- an asexual type of reproduction that is more commonly referred to as apomixis. Magically as it seems, not many plants have this trait.

“The new discovery gets to the same result as apomixis, although by a different route,” said Chan.

In their study in 2010, he and his colleagues demonstrated that they could produce Arabidopsis thaliana that contained only sets of genes from one parent. The whole process was done by crossing a plant with engineered strain that carried a modified version of CENH3- a gene in the centromere that is responsible for correct chromosome segregation- with the mutant MiMe that produces diploid clonal gametes.

After fertilisation, in up to third of the progeny (34%) produced, the chromosomes carrying the modified CENH3 were eliminated, yielding diploid seeds that were genetically identical (i.e. clones) to one of the parents. At last, we are now able to suppress the natural recombination of genomes that occurs during sexual reproduction.

Sadly, this technique does not fully recapitulate apomixis as it still involves fertilisation between two plants. But a possible way to deal this requirement is to generate plants that produce either mutant MiMe or dyad proteins and the genetically engineered CENH3 gene in their reproductive tissues.

If we could apply this technique in major food crops such as lettuce and tomato, we would be able to suppress the natural recombination of their genomes that occurs during sexual reproduction. Thus, beneficial traits such herbicides and frost resistance, insect infestation tolerance as well as better nutritive content could be maintained with no loss of hybrid vigour through successive generations. The cost of crop production would also be greatly minimised when using this technique.

Cloning plants through seeds is indeed a potent tool to propagate cultivars that can retain their original genetics through generations. In a decade or two, if not in a few years, this technique could profoundly change the way essential food crops are produced today, and this could as well be the future of agriculture.

References
1.      University of California- Davis 2011, Plants cloned as seeds: Hybrids that breed true would be a major advance for crop plants, ScienceDaily, viewed 13 February 2012, <http://www.sciencedaily.com/releases/2011/02/110217141315.htm>.
2.      Reece, JB, Meyers, N, Urry, LA, Cain, ML, Wasserman, SA, Minorsky, PV, Jackson, RB & Cooke, BN 2012, ‘Exploring Fruit and Seed Dispersal’, Campbell Biology, 9th ed., Pearson Australia Group, pp. 832-838.
3.      Marimuthu, MPA, Jolivet, S, Ravi, M, Pereira, L, Davda, JN, Cromer, L, Wang, L, Nodue, F, Chan, SWL, Siddiqi, I & Mercier, R 2011, ‘Synthetic Clonal Reproduction Through Seeds’, Science, viewed 13 March 2012, <http://www.sciencemag.org/content/331/6019/876>.
4.      Ravi, M & Chan, SWL 2010, ‘Hapoloid plants produced by centromere-mediated genome elimintation’, Nature, 484, viewed 17 March 2012, <http://www.nature.com/nature/journal/v464/n7288/full/nature08842.html>.
5.      Ledford, H 2011, Genetic engineering brings cloned crops closer, Nature Publishing Group, viewed  13 March 2012, <http://www.nature.com/news/2011/110217/full/news.2011.102.html>.
6.      Bicknell, RA & Koltunow 2004, ‘Understanding Apomixis: Recent Advances and Remaining Conundrums’, The Plant Cell, viewed 17 March 2012, <http://www.plantcell.org/content/16/suppl_1/S228>.
7.      Jolivet, S, d’Erfurth, I, Froger, N, Catrice, O, Novatchkova, M & Mercier, R 2009, ‘Turning Meiosis into Mitosis’, PLoS Biol, viewd 17 March 2012, <http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1000124>.
8.      Mosquin, D 2010, Arabidopsis thaliana, viewed 18 March 2012, <http://www.botanicalgarden.ubc.ca/potd/2010/03/arabidopsis_thaliana_4.php>
9.      Chan, SWL 2011, Chan Lab, viewed 18 March 2012, <http://chan.openwetware.org/Research.html>


Human MIlk


Human Milk
As we know, the concept of breastfeeding is vital to a child’s physical and mental development as it contains nutrients which no artificial formula can provide. Infants that are breastfed have a smaller chance of being diagnosed with illnesses (Queensland Health 2011) So the importance of breast milk can be seen, however these benefits are not just for infants. Breast milk is comparatively healthier and more nutritious for adults then bovine(cow) milk. As breast milk is not readily available for consumption, scientists in china have been able to 'genetically modify cows to produce human milk'.(Gray 2011)

To create cows that are able to produce 'human milk,' scientists cloned human genetics which where then added specifically into the DNA of Holstein dairy cows using a process called electrotransformation.(Yang 2011) Once these embryo's had been genetically modified with human genes, they were placed into surrogate cows. Once the genetically modified cows where born it was found that their milk contained lysozymes, lactoferrin and alpha-lactalbumin, which are all proteins that are found in human milk and have numerous health benefits.(Gray 2011)






One Step Closer to Unlocking the Secrets of Schizophrenia and Bipolar


Recent advances in technology have led to the uncovering of multiple genetic variations that cause two debilitating disorders, Schizophrenia and Bipolar together with a previously unknown relationship between the two.

Schizophrenia, sometimes referred to as a split personality disorder, is a mental illness that affects around 1% of the world’s population [1] and yet little is known about the causes [2]. Bipolar, a mood disorder, affects about the same percentage of the population and is characterized by severe mood swings [3]. Until recently, it was thought that these two disorders were just that, two different disorders.

Although little is known about the causes of these two disorders, it is apparent that they both run in families, indicating that these illnesses are inheritable.


When DNA is being replicated, mutations can arise and cause alteration in the structure of the chromosomes. As schizophrenia and bipolar were found to be inheritable, these mutations caused during errors in DNA replication would play a significant role in the appearance of these disorders.


Chromosomes can be mutated as a result of four different errors during this process. The four errors are deletion, duplication, inversion and translocation. Deletion is where a segment of the chromosome is removed, where as duplication is the opposite, a segment has been repeated [4].
Inversion occurs when the code is copied, but a section is reversed and in translocation, a segment of the chromosome is switched with a non-homologous chromosome (A chromosome that differs from the original).

The studies published in the 43rd volume of Nature Genetics focused on looking at the entire genome of subjects. A task that on paper does not seem like much but in reality is herculean, as a human genome is made up of roughly 3.4 billion base pairs [5]. Such a task was impossible until recently when technological advances in computer processing gave computers the ability to handle such a large amount of information.


The study on Schizophrenia was able to identify seven different genetic variations that were present in Schizophrenic patients, five of these seven being new [6]. This indicated that multiple different combinations of genetic mutation cause this illness, not just one isolated mutation.

Similarly the study on Bipolar aimed to isolate the genes directly related to the bipolar disorder as opposed to that of schizophrenia. The bipolar study used around 17,000 participants, with just over half of the individuals suffering from the disorder. This study was able to identify multiple pathways that led to the presence of Bipolar disorder in subjects.

Combined, the two studies uncovered an overlap in the genetic various leading two both debilitating disorders.
The main link was found within a gene, CACNA1C [7], which was first linked to Schizophrenia, but which after the recent study was also identified as taking a part in the manifestation of bipolar disorder.

By discovering that these two disorders are related, it is possible that in the future, with focussed research into that common area some form of treatment could be formulated to better manage both of these disorders.



Reference List:

[1] MedicineNet, 2012, Schizophrenia, viewed 15th March 2012,
<http://www.medicinenet.com/schizophrenia/article.htm>

[2] Frankenburg, F, 2012, Schizophrenia, viewed 15th March 2012,
<http://emedicine.medscape.com/article/288259-overview>

[3] MedinceNet, 2012, Bipolar Disorder (Mania), viewed 15th March 2012,
<http://www.medicinenet.com/bipolar_disorder/article.htm>

[4] Reece, J, Meyers, N, Urry, L, Cain, M, Wasserman, S, Minorsky, P, Jackson, R, Cooke, B 2011, Campbell Biology, 9th edn, Pearson Education, Australia

[5] Lanthier, C, 2008, How big is the human genome?, viewed 15th March 2012,
<http://nature.ca/genome/03/a/03a_11a_e.cfm>

[6] 2011, ‘Nature Genetics’, Genome-wide association study identifies five new schizophrenia loci, Vol.43,  no.10, pp. 969-976,
<http://www.nature.com/ng/journal/v43/n10/full/ng.940.html>

[7]
2011, ‘Nature Genetics’, Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4, Vol.43,  no.10, pp. 977-983,
<http://www.nature.com/ng/journal/v43/n10/full/ng.943.html>