Finding causative needle in genomic haystack -- Interview with Samuel Tsang about drivers of Pancreatic Caner!!

Pancreatic cancer is the deadliest kind, with only 5% people surviving after 5 years from diagnosis. Many celebrities including Steve Jobs and Patrick Swayze succumbing to it. Pancreatic cancer, like any other, is a heterogeneous disease with many cell and gene of origins leading to its development and spread. But how can doctor find out the cause behind his patient's pancreatic cancer. Could there be a fast and efficient way to screen for the causative needle in the genetic haystack.

Samuel Tsang and his colleagues wanted to develop a method that could do exactly that. They develop a mouse model based protocol capable of testing the cancer causing capacities of genetic variations within a human patients. To know more about the technique, please listen it.



Please refer to the following article for more information:
Functional annotation of rare gene aberration drivers of pancreatic cancer.
Tsang et al., Nature Communications, Jan. 2016.

Engineering a Wolverine!! -- Interview with Junsu Kang about regeneration specific regulatory elements!

Let's imagine you are the scientist responsible for engineering a human into a mutant capable of recovering from any and all injury, like Wolverine. You would need to 'program' his genetic content to do a few things. Firstly, his body has to recognize the injury rapidly and respond to it strongly. Secondly, it should produce a potent healing genetic network, which will mostly include cell proliferative genes. Thirdly, but most importantly, this program has to be tightly controlled so that it does not have background leakage making his body defective and giving him a zillion cancers in the process. Seems like a stretch, doesn't it!

Well, seems like the puzzle might not be so enigmatic after all. Regulatory elements in our genome control gene expression in temporal and spatial manner. If one could isolate regions that are capable of tightly controlling expression between injury and recovery period, then one could use them to drive 'helpful' healing networks for enhancing regenerative abilities, without the side-effect of inducing cancer. But is it possible? Junsu and colleagues show us how to identify and characterize such regions! Please listen in to know more.


For further information, please refer to:
Modulation of tissue repair by regeneration enhancer elements.
Kang et al., Nature 532, 201–206 (14 April 2016)

A cubist view of organogenesis - Interview with Chen-Hui Chen and Matt Foglia about multicolor imaging in zebrafish!

Skin is possibly the most commonly injured organ, while heart injury is the most fatal. Our skin, a barrier that protects from the harshness of the outside world, is easily bruised and scratched - remember bumping into table edges; while heart attacks kill more than 15 million people annually. Understanding the development, maintenance and regeneration of these organs would help deal with such calamities better.

Chen-Hui Chen and Matthew Foglia along with their colleagues set out to so. They study zebrafish skin and heart to understand the cellular behaviors in multiple contexts, but they do so with a colorful twist. They transform into cubist artist, like Picasso, and paint the various cells constituting the organ with vibrant colors. This gives each cell its own identity, allowing vivid observations on how the various components of the organ are interacting with each other. Such interactions lets them paint (pun intended) pictures with precise cellular resolution, opening the path for studying a multitude of biological questions. Please listen in to understand the magic and its implications.




To know more, please read the following:
Multicolor Cell Barcoding Technology for Long-Term Surveillance of Epithelial Regeneration in Zebrafish
Chen CH et al., Developmental Cell 2016.

Multicolor mapping of the cardiomyocyte proliferation dynamics that construct the atrium.
Foglia MJ et al., Development 2016.

Introduction and closing remarks by Priyanka Oberoi.

Shaping the microbiota: Long-lasting effects of antibiotics and talking via miRNA - Interview with Katri Korpela and Shirong Liu!

A human body is not only made up of eukaryotic cells, but lives in symbiosis with almost an equal number of bacterial cells. This rich collection of bacteria co-existing with our body is called microbiota. Specifically, the gut microbiota - bacteria living in our intestines -find insights into the relationship are of special importance since they can shape metabolism, mood and susceptibility to diseases. How is this colony of bacteria regulated forms the basis of this two-part podcast.

In the first part, we talk about the effects antibiotics could have on microbiota. The Microbiota is set up at birth. In kids, the microbiota is highly dynamic, and settles into stable colony by adulthood. What happens when the process of microbiota formation is afflicted by antibiotic usage. Does it ever recover back to normalcy following antibiotic exposure. Katri Korpela and colleagues set out to study the long term relation between antibiotics and microbiota in Finnish pre-school children. Listen in to find insights into the relationship.

In second part, we talk to Shirong Liu who along with his colleagues found the communication device used by our body to stabilize microbiota colony. Microbiota stays stable over long periods of time in adult individuals, and they looked at the role played by miRNA in the process. miRNA are small RNA molecules that regulate gene expression. Liu and colleagues found that our body uses miRNA to shape the microbiota diversity and such miRNA can be detected in fecal samples. This interesting finding opens the door to non-invasive diagnostic devices to look at health and composition of microbiota. Please listen in to find more!!


To know more, please refer to the following articles:

First part (Antibiotics and microbiota):
Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children
Katri Korpela et al., Nature Communications 7, Jan 2016

Second part (Regulation by Fecal miRNA):
The Host Shapes the Gut Microbiota via Fecal MicroRNA
Shirong Liu et al., Cell Host and Microbes, Volume 19, Issue 1, p32–43, 13 January 2016

Introduction and closing by Priyanka Oberoi.

SPARCing the ECM - Interview with Meghan Morrissey

Cancer cell metastasis is one of the most important factor that worsens disease prognosis. During metastasis, cells invade blood vessels and other tissues by first passing through a barrier of extra-cellular matrix: a wall of structural components surrounding all cell types. How are cells able to achieve breakdown and invasion of this wall?

Meghan Morrissey and her colleagues started to look at the role played by SPARC family of genes in the process. The SPARC family has been implicated to play a role in cell invasion, but its exact nature was unknown. Using a model of anchor cell invasion in C. elegans, she elegantly and beautifully provides insight into the link. We talk with her to know more.



Please read the original article here:
SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane  
Morrissey et al., PLoS Genet 12(2): e1005905, 2016. 

A fat hope for autism! - Interview with Zhigang Xie on role of fatty acid metabolism in neuronal stem cells.

Autism is a distressful condition with impaired social interaction and communication. At its basis, it is a neurodevelopment disorder, with certain areas of the brain not developing properly. The burden of brain development falls on neural stem cells, which divide to generate functional neurons as well as maintaining their own numbers. Zhigang Xi and his colleagues show that fatty acid beta-oxidation seems to play a major role in maintaining the stem cells involved in autistic behavior. How is this achieved -- to know the answer, we call Zhigang Xi.


Please read the original article here:
Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism
Xie et al., Cell Reports (2016). Volume 14, Issue 5, p991–999.

A coin toss for being fat! -- Interview with Kevin Dalgaard about the role of an epigenetic switch for obesity

Obesity is a growing epidemic in the world. Development of obesity involves environmental factors like eating choices (McDonalds vs. salad) or exercise, and genetic players. But if we were to keep all the variables the same, like two twins being given the same food, would they both end up with the same body shape??

Surprisingly no!

Kevin Dalgaard from Max Planck Institute of Immunobiology and Epigenetics and colleagues from around the world show that shows that even if two genetically identical people are given the same food, one might end up being lean and the other fat -- and this 'decision' lies in an epigenetic network on top of which sits Trim28. Trim28 network acts as a coin toss, with chance deciding the network's strength and thereby development of obesity.
To understand this amazing regulation better, we talk with Kevin.


Please read the following article to know more:
Trim28 Haploinsufficiency Triggers Bi-stable Epigenetic Obesity
Dalgaard et al., Cell (2016). Volume 164, Issue 3, p353–364.

You can also a YouTube video explaining the article here: Who am I not?