JAK-STAT pathway: hacking protein regulation

So the JAK-STAT pathway, as with all pathways, have different functional effects. It is associated with cancer, immunodeficiency, growth retardation and many more.

different ligands induce the phosphorylation of different STAT residues. This increases provides a regulatory mechanism on the downstream signals. It is fascinating to see the different ways in which cells regulates proteins.

It would be interesting to utilise the cells method in controlling and understanding cellular function. This can be extrapolated to obtain therapeutic methods for the diseases associated with the JAK-STAT pathway or it can be used to counter bacterial infections.

I would like to know the differences between the phenotype and genotype between JAK-STAT caused diseases and those diseases with other causes.

Review: http://www.annualreviews.org/doi/full/10.1146/annurev-med-051113-024537

Protein structure of the JAK-STAT receptor. Image obtained from http://www.niams.nih.gov/Research/JAK-STAT_Meeting/

The importance of fly hearts

The drosophila (fly) had been, and still is, an important model organism in science.

There are developmental similarities between drosophila and vertebrate heart development. From lineage tracing and genetic testing, there are homologues to the drosophila gene found in the human genome responsible for heart development. Since it is relatively easy to view and manage drosophila in the lab. The drosophila could be induced to model a specific cardiac disease and taking into account age-related or nutrition-dependent effects.

During the third instar of drosophila development, the heart is innervated and has its own pacemaker. At this stage the heart can be extracted and utilised to test the physiological conditions.

An interesting paper (Zhou et al. 2009), discovered that cardiomyocyte are derived from epicardial progenitors. The implications of this study suggest it could be utilised in cardiac repair and regeneration.

The next experiment should determine whether the epicardial cells can be induced in foetal mice hearts as a regenerative mechanism or whether the epicardial cells are necessary for cardiomyocyte development.

Review: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551295/#R181
Primary paper: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574791/

Wt1-derived cells differentiate into cardiomyocytes. image obtained from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574791/

Get rid of background noise!

Sir Tim Hunt explained the complexity that arises in biological organisms in the most eloquent ways. His statement was based on the evolution of species. The previous basic pathways used to perform the task is 'replaced' efficient pathways of performing specific tasks. The basic task is actually not replaced, it is just not used, it fades into the background. But, nevertheless, it is always there. This is what make the cell a complex structure. 

As a researcher you need to know how to focus on the pathways that matter and not to be deterred by the background pathways. Going along this logic, I believe this same mindset should be used when determining the auto-immune diseases. (I have not yet checked the literature to assume that this mindset has not been used). 

The immune system is already a complex one, if we are able to extract the essential proteins involved in the disease then I believe it would lead to a quicker understanding of what goes wrong in autoimmune diseases such as myasthenia gravis. 

Image obtained from http://www.outofthewoodsnutrition.com/blog/2015/7/15/10-things-you-need-to-know-about-autoimmune-disease

Kill cancer cells?

Targeted apoptosis of cancer cells.

Tumour necrosis factor is a ligand the binds to the TNF receptors and activates downstream signalling pathways.

An interesting characteristic about the TNF signalling pathway is that they activate inflammatory-genes and it also induces apoptosis.

This might be a potential therapeutic target for cancer. By directing the gene or protein to specific tumour cells. It will be more specific than chemotherapy and more effective. The transmission method could be through retrovirus or a mechanism that pathogens utilise to enter the cell.

Function of TNF. Image obtained from http://www.sciencedirect.com/science/article/pii/S0165614710002105

review - http://www.nature.com/cdd/journal/v10/n1/full/4401189a.html

Zebrafish Regeneration

Zebrafish are model organism used in Biomedical Science. One of the used is to observe how the cellular and molecular processes influence their regeneration.

An interesting thing is that the fin can regenerate. Epithelial cells are the first type of cells to cover the wound and then other cells differentiate into the fin structures.

It also regenerate its heart. The implications are great. If we can induce pluripotency in differentiated cells. then we can induce regeneration in heart cells, especially in humans. But first, we need to understand the molecular cascades that are responsible for regeneration.

The beauty of biology is that the cascades to achieve an effect are similar. Consequently, when we deduce how regeneration is induced in the heart. It will make regeneration of nerve cells relatively simpler.

There is an interesting paper that looked at heart regeneration. They genetically ablated muscle cells. This is really impressive because there is no injury induced on the surrounding cells, as seen in lesions. This increases the specificity of the ablation. They also labeled the surrounding cells, in order to trace the origin of the regenerated cells. Regeneration was observed by fluorescence and electrophysiology.

They should experiment genetic ablation in mammals, to see whether it would induce a slight regeneration. I think KO experiment of known genes should be done in conjunction with the ablation studies to determine which genes are responsible or influence regeneration.

Review: http://www.sciencedirect.com/science/article/pii/S0168952513001133
Primary paper: http://dev.biologists.org/content/138/16/3421

Rapid regeneration of ventricular cardiomyocytes after ablation-induced injury. Figure obtained from http://dev.biologists.org/content/138/16/3421

Aims and objectives

My Aim is to at least have one post per week about science and an idea. The idea will be a hybrid of two different concepts.

The objective of the project is to:

• develop creative and innovative thinking
• being up-to date with current research
• develop an interest
• improve my critical thinking of papers
• enhance my writing skills

Well, let's start this journey, innit?