Wedding :)

No podcast this week since I get hitched to this beauty - Priyanka Oberoi ;)

Next two weeks, we return with complex disorders: autism, obesity, cancer and microbiota!
Stay tuned :)

Tough times don't last; 5' uORFs do! -- Interview with Shelley Starck about Cell's Stress Response Mechanism

What do you do when you feel stressed and sick. Probably try to get some rest and sleep, eat healthier and maybe go to a doctor. Did you know that individual cells in our body also come under stress! And they respond as you and I do: they decrease energetically expensive protein synthesis (rest),  but increase production of things that help them fold proteins properly, like chaperones and heat shock proteins (develop healthier mileu), and try to contact neighboring cells and immune response (doctor) to tell about their condition. But how do they achieve all these amazing tasks???

Shelley Starck, a former post-doc with Nilabh Shastri, and currently a post-doc with Peter Walter at UCSF set out to answer this exact question. She developed a highly sensitive method of detecting proteins within the cell and used the assay to find those that increase during stress. What she found can be summarized by a quote from annonymous source: "Good things can come from unexpected places".

What are these good things and how do they arrive, listen in!!!



Please read the article for more information:
Translation from the 5′ untranslated region shapes the integrated stress response
S. R. Starck et al.,Science 351, aad3867 (2016). DOI: 10.1126/science.aad3867

Give me food, give me sex; give me that which I desire -- Interview with Yi Li about reward sensing!!

Chocolate, chips, cigarettes, alcohol, sex; well, we all choose our sins. What is making us crave for such desires, and what happens when we finally achieve them. Yi Li in his exciting study published in Nature Communications shows that serotonergic neurons in the dorsal raphea nucleus in brain might be involved in reward and pleasure behavior. He did this by observing and recording neuronal activity in live, uninhibited mice while they seek food, sucrose, social interaction and even sex. We call him to hear more about this exciting study.   

You can read the original article here: 

Serotonin neurons in the dorsal raphe nucleus encode reward signals

Li et al., Nature Communications 7, 10503, January, 2016.

Selfish beta-cells and Motor Neurons going both ways - Chat with Theresa Hartmann

You might have all heard about the 'Selfish gene', the groundbreaking unconventional hypothesis published 40 years ago by Richard Dawkins. But, did you know that cells can also become selfish under stress.
Theresa Hartmann summarizes an article, Evidence of β-cell Dedifferentiation in Human Type 2 Diabetes, that suggests that β-cells - the cells that produce insulin for regulation of blood glucose and whose defects lead to diabetes, could act selfishly under stress!!
β-cell stress can occur due to large workload thrust upon them due to obesity or insulin resistance -  the case where body organs cannot properly sense insulin and thus demand more of it. This makes them sick over time and ultimately kills them. To escape this adverse end, a few of these cells lose their identity; they 'forget' who they are supposed to be; and become something else. They no longer sense metabolic stress and can continue to survive. Of course, this occurs at the cost of the person's health which deteriorates faster from even lower β-cell mass.

Next, I help summarize a fascinating discovery that might upturn hundred year old belief. It has been always thought that motor neurons -  the cells that connect the brain to the muscle, only pass signals in one direction. They act as passive relays of the message from the information and processing centers to the acting musculature. But new research, Motor neurons control locomotor circuit function retrogradely via gap junctions, suggests that this might be so simple. The article suggests that the motor neurons are connected to the upstream processors with gap junctions - proteins that connect the cytoplasm of two cells allowing free movement of molecules and ions between two cells. Such connection allows motor neurons to communicate, and control, the activity of higher processing units, thus making the connection from brain to muscles two directional.

Please have a listen!

In case of heart problems, call 1-800-BMP-Caveolin - Interview with Chi-Chung Wu and Jingli Cao

Today our attention turns to heart disease, one of the leading cause of death in the world. Upon heart attack, cardiomyocytes, or the heart muscle cells die off, and this loss is irreversible. As time passes, the lack of heart muscle stresses the organ finally leading to failure. On the other hand, zebrafish posses extraordinary capacity to recover from strong cardiac trauma. We talk to two scientists, Chi-Chung Wu from Ulm University and Jingli Cao from Duke University, who have recently shown how the zebrafish is capable of doing so.

Both the studies share certain commonalities:

Firstly, in order to understand the system they both use novel cutting edge methodology to look at RNA – the middle man between DNA, the information component of the cell, and protein, the functional component of the cell. While Chi-Chung probes the RNA landscape to find genes involved within the heart cells at the injury site, Jingli looks at RNA content within single cells of the epicardium, a sheet covering the heart wall.

Secondly, both authors find factors that are dispensible for development, but become initiated by tissue damage and are necessary for successful recovery. One might think the extraordinary capacity of the zebrafish to regenerate its organs might lie in such genetic differences post-injury. To learn more about the process, please listen to the podcast.

To know more about the work, please read the articles:

Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration.
Wu, Kruse et al., Developmental Cell, 2016, 36-1: p36–49.

Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration.
Cao et al., Development, 2016 143: 232-243.

Cheaters Make Co-operation Robust!

Which of these is true??

1. You need rational beings with minds to have teamwork.
2. Bacteria and yeast, organisms without brain, cannot collaborate for the good of each other.
3. Cheating individuals destroy co-operation in the society, and crash its existence.

If you thought that all were false, you might be in for a surprise!

We do have limited resources in this world. And for our survival, correct utilization of those resources based is of utmost importance. Many people can co-operate peacefully with each other to manage resource use. 

But what happens when a few people start to cheat, and greedily take more than their fair share without contributing to the general good. One would think this would cause havoc and destroy the delicate balance of co-operation among individuals, finally leading to population crash. 

Unexpectedly, Adam Waite in his work performed at University of Washington found otherwise. He simulated population dynamics between co-operative and cheating individuals sharing limited resources, and excitingly found that the population became more robust to crashes. 

To understand this exciting and interesting finding, lets call him up!

To know more about the work, please read the article:
Defectors Can Create Conditions That Rescue Cooperation
Waite et al., PLOS Computational Biology 11(12): e1004645, December, 2015.

and the blog:
Cheaters allow cooperators to prosper

How we sense hunger? Interview with Zhiying Li.

What tells our body that it needs food?? The answer might lie within the working of a hormone called leptin. The hormone, mostly secreted by fat tissue, works on a small area of the brain, the hypothalamus, to control hunger and satiety. Its decrease leads to over-eating and obesity. Now, Zhiying, a post-doc in Jeffery Friedman's Lab at Rockefeller University, finds that the molecule might have a brother-in-arms for control of such feelings. In her article published in Cell Metabolism, she finds that another peptide hormone, amylin, works in concert with leptin and enhances its effect. Combinational therapy with both amylin and leptin seem to have better effect on controlling obesity. We ring her up and try to find more about this new synergy!


Read the article for yourself:
Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake
Li et al., Cell Metabolism, Dec. 01, 2015.