An alternative speculation to the origin of Life?

The endosymbiosis theory postulates that the mitochondria of eukaryotes evolve from an aerobic bacteria. In recent times, the discovery of the Mimivirus was hailed as a missing link between a virus and a bacteria. However, it is also a fact that the Mimivirus possesses a genome of a size that is comparable to the other bacteria. The mimivirus also possesses genes that are involved in nucleotide and amino acid synthesis, which some bacteria lacked. It also possesses an inner lipid membrane. I was speculating on a model of endosymbiosis whereby the ancestral virion particle like the mimvirus enters a prokaryotic cell. This virus may have accumulated mutations resulting in a defect in assembly of viral coat. As it may have coded for genes that may be beneficial to the prokaryote, it forms a symbiotic relationship with the host. It may be possible that the virus is the ancestor of the nucleus in a modern day eukaryotic cell. Like a nucleus, it can take over the role in controlling the cells.

Mimivirus, the hope for medicine?

The Mimivirus is the largest known virus known to mankind. It has a size of up to 600 nm. Another amazing thing about this virus is that it harbors a level of complexity which brings it closer in relation to our modern cells, with 911 genes (Prescott, 1993) encoding proteins like the amino - acyl tRNA synthetases, DNA polymerases and other metabolic enzymes. The size of its genome is 1.2 megabase (La Scola et al, 2003). Perhaps the size of the Mimivirus virion is large enough to deliver a human minichromosome into the cell. However, the capsid needs to be engineered in such a way that it can bind to receptors of specific cells. Another challenge would be to package the minichromosome into the viral capsid. If the artificial chromosome is going to be the next thing in gene therapy, the search for a nanoparticle that can act as its carrier continues.

Citations
1) Prescott, L. (1993). Microbiology, Wm. C. Brown Publishers

2) La Scola B, Audic S, Robert C, Jungang L, de Lamballerie X, Drancourt M, Birtles R, Claverie JM, Raoult D. A giant virus in amoebae. Science. 2003 Mar 28;299

Study of the effects of trans-acting factors encoded by viruses

The proteins encoded by viruses can affect the cell in more ways than one. Thus, it would be interesting to study the long term effects of trans-acting factors encoded by the viruses on cells. One approach may be to integrate the virus's genome into that of the cell's like how a normal virus would infect a cell. The problem is that the virus may integrate in a location within genome whereby the integrated viral DNA element may affect the function and expression of neighbouring genes. In the end, our observations may be affected. I was wondering if it is possible to introduce an artifical chromosome with an integrated viral element instead. It would allow us to study the effects of trans-acting elements encoded by the virus on cells' functions and the long term effect on the cell.

New drug delivery methods delivered at delivering artificial chromosomes aimed at gene therapy

The use of viral vectors in gene therapy has a severe setback - the risk of cancer. Understandably, viruses have potent promoters and if integrated into a region where an oncogene is found, there is a possibility that cancer can arise. The use of artificial chromosome is attractive as it doesn't disrupt the original genome of the cell and is also capable of replicating. However, it's may be too big to be packaged into viral particles. The advantage of having a viral nanoparticle is its target specificity. However, research on nanoparticles is currently ongoing and before long, we may have a nanoparticle large enough, but having the properties of viral protein coats for target specificity in order to deliver the artificial chromosomes into mammalian cells. I think the artificial chromosome is the future direction of gene therapy but "drug" delivery methods have to be worked on.

Citations
1) New cancer case halts US gene therapy trials. http://www.newscientist.com/article.ns?id=dn3271

2) Human minichromosomes. http://bric.postech.ac.kr/science/97now/01_5now/010504c.html

Artificial chromosomes and their promise in research

Genetics research has come a long way since the discovery of the DNA double helix by Watson and Crick. It's now possible to construct mammalian artificial chromosomes. Ways have been discovered to induce stable gene expression from a mammalian artifical chromosome (Grimes et al, 2001). There have also been improved methods in delivery of artificial chromosomes to mammalian cells (Chen et al, 1997). Indeed, it's a great way to study trans-acting factors being expressed on a long term basis WITHOUT disrupting the original genome in cell-lines.

Citations
1) Grimes BR, Schindelhauer D, McGill NI, Ross A, Ebersole TA, Cooke HJ. Stable gene expression from a mammalian artificial chromosome. EMBO Rep. 2001 Oct;2(10):910-4.

2) Chen M, Compton ST, Coviello VF, Green ED, Ashlock MA. Transient gene expression from yeast artificial chromosome DNA in mammalian cells is enhanced by adenovirus. Nucleic Acids Res. 1997 Nov 1;25(21):4416-8.

The Civil Servant in the Emperor's court

I was inspired to write this post when I came across this piece of writing on Du Fu the poet on answers.com. http://www.answers.com/topic/du-fu

(born 712, Xiangyang, China — died 770, Hunan) Chinese poet, often considered the greatest of all time. After a traditional Confucian education, he failed the important civil service examinations and consequently spent much of his life wandering, repeatedly attempting to gain court positions, with mixed success. His early poetry, which celebrates the natural world and bemoans the passage of time, garnered him renown. He suffered periods of extreme personal hardship, and as he matured his verse began to express profound compassion for humanity. An expert in all the poetic genres of his day, he is renowned for his superb classicism and skill in prosody, though many of the subtleties of his art do not survive translation.

A renowned poet, yet I found it surprising that his ambition was to be a civil servant in the emperor's courts, hence my musings on the mind of a civil servant in the emperor's court as shown below:

I, as a civil servant in the Emperor's court acknowledge that:

1) The Emperor is the dragon and he is my overlord.

2) I am also subserviant to the empress dowager.

3) The emperor's son will be the next in line to the throne.

4) If I am under a minister, I have to serve him with unquestioning loyalty.

5) I am prepared to be punished for violating any part of the system that was put into place.

6) I have to pass important examinations if I want to be appointed in leadership roles.

7) Scholars who did better than me in the important examinations would be appointed as officials holding positions that are higher than mine.

8) A degree holder will not necessary be appointed to a civil service position.

9) Someone with a higher classification of degree will stand a better chance at appointment in the civil service than me.

10) This examination system is meritocratic.

11) The values of Confucianism in running the country.

Virology and oncology

It is known that viruses produce potent activators as well as repressors. An example of a potent transactivator is Tat, in the case of HIV viruses. These transactivators are known to increase the expression of viral genes. However, if such activators are integrated in the vicinity of an oncogene like Ras or Myc, there lies a possibility of transformation. Tat itself has a repressive function on p53, a tumor suppressor (Harrod et al, 2003). Thus, investigating the implications of viral activators and repressors on tumorigenesis is an interesting field. Using a viral vector, a gene encoding an oncogene can be joined TOGETHER with the attenuated viral genome (can synthesize activator proteins, but not others like the viral protein coat) to investigate the effects of the virus' activator function on the oncogene's expression. To investigate the effects on tumor suppressor, the gene encoding the tumor suppressor should be joined together with the attenuated viral genome (can synthesize repressor proteins, but not others like the viral protein coat) and homologous recombination with the wild type tumor suppressor within the genome should be carried out. This is to simulate the event in which the virus integrates itself in the vicinity of the tumour suppressor.

Citations

1) Harrod R, Nacsa J, Van Lint C, Hansen J, Karpova T, McNally J, Franchini G. Human immunodeficiency virus type-1 Tat/co-activator acetyltransferase interactions inhibit p53Lys-320 acetylation and p53-responsive transcription. J Biol Chem. 2003 Apr 4;278(14):12310-8.