No man left behind! Interview with Judith Yanowitz on faithful DNA segregation during meiosis.

DNA is the strand that connects generations of life. It contains the information needed for all phases of life, and that information needs to be faithfully passed on to the off-springs for the specie to continue. In multiple organisms, this information is divided into chromosomes, and each of these chromosomes need to be copied and separated equally during germ cell formation. Any disturbance in the logistics of chromosome separation can leave one of the two daughter cells with less or more material, which can be detrimental.

How does the cell ensure proper logistics during the process? How does it know when the separation process has started and when each and every chromosome has been successfully separated? It's not a simple counting process since the number of chromosome differs between species, with humans having 23 sets, but our close relatives, chimpanzees and ape have 24 pairs. How does the cell adapt to this diversity. Tyler, Rana, Judith and colleagues ask this question and find a very interesting mechanism guiding the process. They find a surveillance mechanism that starts as soon as the first chromosome starts information exchange, and lasts until the last one finishes, thereby ensuring that the process only proceed after its faithful completion. To understand the details, please listen to the interview with Judith.


To know more about the work, please read the following article:
A Surveillance System Ensures Crossover Formation in C. elegans
Tyler and Rana et al., Current Biology, 2016

Food for Eye! Interview with Tiago Santos-Ferreira on cell-support paradigm for retinal transplantation!

Cell-transplantation based therapy is increasingly becoming relevant these days, esp. with a bloom in techniques for stem cell and organoid production. The transplanted cells could greatly benefit treatment of degenerative diseases. But how do the transplants help the diseased organ. The obvious thinking is that they help by providing a fresh supply of healthy cells. But is that always the case?

Tiago and colleagues asked what happens to retinal cells transplanted into a damaged eye. And surprisingly found that the transplanted cells did not integrate into the organ, but rather provided cytoplasmic material to the pre-exisiting host cells. Cytoplasmic material present within the transplanted cells was being taken up by the host cells. This was a clear indication of a new way by which transplants could help the damaged tissue, which could be used to potentially transfer much more cargo in future. To know more, please listen to Tiago.  


For further information, please refer to:
Retinal transplantation of photoreceptors results in donor–host cytoplasmic exchange.
Santos-Ferreira et al., Nature Communications, 2016

Packaging without packets! Interview with Shamba Saha on membrane-less organization within cells!!

How do you organize your stuff at home. In boxes, I suppose. Tucked into boxes, all the stuff is nicely arranged. This is not special to human behavior, as even biological cells use the same principle of compartmentalization! They organize the information source (DNA) into nucleus, making it efficient to read and copy. They put all energy forming apparatus into units called mitochondria. They organize garbage disposal into chambers called lysosomes. But the beauty and complexity of biological systems doesn't stop there! They go one step further and aggregate developmentally important and dynamic stuff into structures that lack a membranous boundary; essentially packaging biological entities without an overt packet!

How do they achieve such a feat. Shamba and colleagues try to answer this question by looking at the formation of germline defining particles, the P-bodies, in a worm, C. elegans. These non-membranous compartment, they find, are generated by an striking process called phase-separation, just like oil droplets form when mixed with water! But these bodies are much more than passive emulsions, and are a complex mix of RNA and protein dynamically interacting with the surroundings!! What is even more striking, and beautiful, is that these do not form randomly, but are localized to one area of the cell. How many components are needed to make such a complex biological process?? Listen to Shamba to know that the real beauty in the system is its simplicity, as only one (ONE!!!) protein is enough to generate these structures, and a very small network to regulate it.



To know more about the work, please refer to the following publication:
Polar Positioning of Phase-Separated Liquid Compartments in Cells Regulated by an mRNA Competition Mechanism
Saha et al., Cell. Volume 166, Issue 6, p1572–1584.

Also, you can see a video abstract on the topic here:
Phase separation in cell polarity
  

A morphing traveler. Interview with Mohit Jolly on identity changes during metastasis!

Cancer cells evade foreign tissues during metastasis. This process is most critical phase of cancer development, since it decreases a successful prognostics drastically. During the invasion process, the cells change their characteristics, acquiring different shapes, cell identity and lineage. How this is regulated still remains open question, and vital to developing a cure for the disease.

Mohit and colleagues take an integrated theoretical-experimental approach to understand how sarcomas spread. Sacromas arise from connective tissues, like bone or fat. And while traveling long distances they undergo a change into more epithelial like identity. This plasticity helps the cells survive better in the the body. To more more about such transition, please listen to the interview with Mohit.



For more information, please refer to:
Mesenchymal-epithelial transition in sarcomas is controlled by the combinatorial expression of miR-200s and GRHL2
Somarelli et al., Molecular and Cellular Biology, 2016

The Scent of Jealousy! Interview with Meghan Laturney on mate-guarding behavior!!

You know of Hollywood plots where a man comes smelling of another woman, and his wife suspects him of cheating on her. The woman is relying on olfactory cues for keeping a tab on the guy's sexual behavior. Does this soap-opera behavior also occur in other species? Is smell used as a tool to guard against promiscuous behavior??

Meghan and her colleagues try to tease apart such behavior in the fruit fly, Drosophila melanogaster. They see that the male deposits specific scents on the female's body and inside her reproductive tract. Both these olfactory cues decrease the female's attractiveness to future mating partners. This increases the chances of the male's sperm fertilizing the female. The female, on the other hand, might actively try to remove these marking scent in order to continuing mating, which gives her eggs better to survive. To know more about this exciting arms race between the sexes, please listen to Meghan!


To know more on the topic, please refer to:
Drosophila melanogaster females restore their attractiveness after mating by removing male anti-aphrodisiac pheromones.
Laturney & Billeter. Nature Communications.  7, 12322 (2016)

What did you have for dinner last night? Interview with Vishnu Sreekumar on memory formation in the real world!

Isn't is difficult to remember what you had for dinner two night ago, but so easy to remember your first kiss! Why is it difficult to remember few experiences while other stay etched in our memory forever. Of course, we have limited brain capacity, so few things are removed at the expense of others, but how do we evaluate that information; how much decision making goes into paying attention to important tasks for remembering them later onward.

Vishnu Sreekumar and his team work on memory formation in the real world. They utilize information gathering using contemporary technologies to come-up with models that can explain what we look for in experiences when memories are being formed. Their exciting work not only helps model our day-to-day working, but can also help people with better memory retention and improving attention span. To know more, please listen to Vishnu.


For further information please refer to the following publication:
The Episodic Nature of Experience: A Dynamical Systems Analysis.
Sreekumar et al., Cognitive Science, 23 July 2016.

Piggyback Microbe and Cancer! Interview with Niranjan Nagarajan on role of microbiome in bile duct cancer.

Cancer is a very complex disease, with various genetic and environmental factors playing a role in its development and growth. Mutations within the cell and signaling among cells is well known to play vital roles. But could there be other players involved in the process. Of note, something which surrounds us at all times: our microbiome?

Our body is composed of as many microbiome as our own cells. A lot of it comes from the food we eat and the water we drink. Along with our meals, food related parasites might bring their own microbiome into our body, and these could in turn home into organs and modify the tissue microenviroment. This is what Niranjan and colleagues see for bile duct cancer - in which liver fluke parasite arriving from consumption of raw fish finds a home in the bile duct and increases the chance of developing cancer. Their work emphasizes an appreciation into the role of microbiota in cancer development. To know more, please listen to Niranjan.  



To learn more, please refer to:
Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma
Chng et al., eBioMedicine, June 2016Volume 8, Pages 195–202.

A Mito coup d'cellule! Interview with Hansong Ma on selfish drive in mitochondria!!!

Mitochondria are the power generators of the cell. Each cell has thousands of them, and each has its own genome. The DNA it possesses is needed for survival, and it has to be replicated to generate new ones. This means that mitochondria that can replicate better can out-compete others with replicative disadvantage and, in extreme cases, take over the entire cellular compartment. Since, the cell is blind to such competition, 'bad' or non-functional mitochondria can take over, to their own benefit and to the cell's detriment; thereby leading to 'selfish behavior'. 

This is of particular importance to current human health. UK's decision to allow three-parent baby is a monumental step in curing a set of congenital diseases. In this the defective mitochondria is replaced with that from a healthy donor. But even if a few defective ones remain behind (from among thousands), this also creates a competition among the two populations. And if the selfish drive of the defective one is strong enough, it might again take over the cell, thereby increasing the chance of pathogenesis. A good donor should not only be healthy, but also strong in its selfish drive. To understand how such competition is accomplished, please listen to the interview with Hansong Ma.

For more information, please refer to:

Selfish drive can trump function when animal mitochondrial genomes compete.

Ma and O'Farrell. Nature Genetics 48, 798–802 (2016).

Eat me not! Interview with Anu Chaudhary on cell surface marker regulating autophagy in humans!

Cells are constantly talking with each other, mostly with the help of cell surface receptors and ligands. This includes information on the amount of 'self-digestion' to perform. Higher self-digestion, or autophagy, leads to faster protein turnover and has been implicated in many age-related diseases, esp. those with an autoimmune component. Could we understand the mechanism controlling levels of autophagy and modulate it to affect disease outcomes?

Anu Chaudhary and her colleagues display an elegant way to screen human genetic variation underlying any observable phenomena. By focusing on response to rapamycin, a drug that induces autophagy, they were able to isolate variations that enhance cellular self-digestion. They use this to characterize cell surface receptors that can vary autophagy levels, and use this knowledge to develop means that could deter auto-antibody production. To learn more about the exciting and relevant finding, please listen to Anu.


For further information, please refer:
Human Diversity in a Cell Surface Receptor that Inhibits Autophagy.
Chaudhary et al., Current Biology, 2016.

Music to the heart! Interview with Troy Shirangi on development of neural circuitry for fly courtship behavior!!

You all must have seen a peacock dance. It's majestic, isn't it! The vibrant colors all moving in big waves, but for what?? The male peacock performs the majestic gesture to lure the female into mating. This is true for many species where the male makes ostentatious displays to entice the female. But how does the male develop the displays that the females respond to? Are there special neural circuitry controlling this behavior?? And if so, which genes are responsible for making them???


Troy and his colleagues dissect such machinery for the fruitfly, Drosophila melanogaster. They find the neurons and master transcription factor autonomously controlling the courtship behavior. They are able to specially pin-point the neuro-muscular apparatus underlying male singing. The study lays the platform for understanding sex-specific behaviors and the evolutionary forces underlying mate choice. To understand about the exciting work, please listen to the interview with Troy.


For further information, please refer the following study:
Doublesex Regulates the Connectivity of a Neural Circuit Controlling Drosophila Male Courtship Song
Shirangi et al., Developmental Cell, 20 June 2016.
   

Is to perceive to suffer? Interview with Anjali Krishnan on empathetic pain perception!

Imagine falling on the road and hurting yourself. Now imagine watching the same event happen to someone else. Would you react similarly to both these situations? Would your brain respond alike to your own pain vs. to other's pain. Aristotle once said, 'To perceive is to suffer'. According to him, your reaction would match. But is that true?!

Anjali Krishnan and her colleagues at University of Colorado Boulder set out to find answer to this question of similarities and differences in perceiving self and empathetic pain. Surprisingly, and excitingly, they found that our brain looks at these kinds of pain differently. Empathy for other people's pain involves the process of mentalization: imagining other's situation and condition. To know more about the interesting observation, please listen to interview with Anjali.



To know more, please read here:
Somatic and vicarious pain are represented by dissociable multivariate brain patterns.
Krishnan et al., eLife 2016;5:e15166.

Exercising the old away! -- Interview with Marissa Schafer about exercise decreasing senescent adipocytes!!

We all know the many benefits of exercise, and the evils of fast-food diet. Exercise makes us feel healthy, younger and more vital; while excess of double cheeseburgers gives the lethargic look with tired body. But how exactly does exercise lead to such benefits; and high fat diet lead to such deterioration?

Marissa Schafer and her colleagues at Mayo Clinic asked this simple, yet complex question. What they saw was that high-fat diet was increasing the proportion of senescent fat cells -- cells that are incapable of growing or diving. They saw that such cells were attracting immune system components, that could lead to adverse effects. Exercise on the other hand decreased the presence of such cells, excitingly even in the case of high-fat diet. So, if you have a hamburger, be sure to couple it with a 5k. To know more the exciting study, please listen to the interview with Marissa:


Please refer the following for more information:
Exercise Prevents Diet-induced Cellular Senescence in Adipose Tissue.
Schafer et al., Diabetes 2016.  

One ratio to rule them all! Interview with Leigh Harris about a unified principle regulating bacterial cell size!

We live in a 3D world, in which every object occupies space. Same is true for all cells. The size of biological objects is a ubiquitous property, about which very less is known. How do cells 'measure' their size and how do they regulate it in response to changing environment? These unanswered questions have far-reaching implications on every aspect of biology.

Leigh Harris and her colleagues set out to discover the principles regulating cell size in a simple model, bacteria. She used live imaging and quantitative analysis to accurate measure bacterial cell volume and surface area: two parameters implicated in size control. Excitingly, she was able to come up with a simple ratio: the rate of surface area to volume change, which defines the steady state size and shape of the cell. This presents a novel unified model for regulating bacterial size. Lets call Leigh to understand more about this principle!



To know about the story, please read:
Relative Rates of Surface and Volume Synthesis Set Bacterial Cell Size
Leigh and Theriot, Cell, 2 June 2016.

Not starving to death: Interview with Manqi Wang about glycemic control during fasting!

Have you ever missed a meal, maybe two. But your brain still keeps working, doesn't it. It still keeps getting the glucose it needs to think. Without this sustained blood glucose regulation during fasting, our body can go into a hypoglycemic shock that can be fatal. What regulates such important network.

Manqi Wang and her colleagues investigated the role of autonomous nervous system during prolonged starvation. They interestingly found that the reflex pathways plays an important role. Surprisingly, they see that the system is highly plastic and changes network strengths based on physiological demands. To learn more, please listen to Manqi!



For more information, please refer to:
Fasting induces a form of autonomic synaptic plasticity that prevents hypoglycemia.
Wang et al., PNAS 113.21 (2016): E3029-E3038.

Help fight kid's cancer!!

Kid's cancer might just be the most devastating thing on the planet. Help find a cure by donating a little as Vishnu Sreekumar and I bike to raise awareness. Every penny matters!!!

Please follow our team here (and contribute too :) ):
https://greatcyclechallenge.com/Teams/Letsdothis

Little things that can make a big difference -- Interview with Jane Freedman and Kahraman Tanriverdi about detecting small RNAs in blood!

RNA molecules - most of us might know them as middle men between the biological information storage unit: DNA, and the functional unit: protein. But a large numbers of small sized RNAs are important players in regulating genetic networks. These small RNAs, like micro-RNA, are capable of regulating a vast numbers of genes. These small RNAs are involved in almost every biological aspect, from development to disease. Wouldn't it be interesting to sense their presence to predict developmental or disease trajectories.

Now, Jane, Kahraman and their colleagues develop a sensitive assay capable of detecting and quantifying small RNAs in human blood samples. They use their technique to probe small RNAs presence in human blood samples and to detect their diversity among various groups. Their findings show a great deal of diversity in small RNAs presence, whose role would be most interesting to elucidate. To know more about the study, please listen to their interview:


To know more about the study, please refer to:
Diverse human extracellular RNAs are widely detected in human plasma
Freedman et al., Nature Communications, 2016.

How is more important than What! -- Interview with Jonathan Coloff about Glutamate usage during function vs. proliferation!!

Cells perform their function: like heart muscle makes the heart beat or beta-cells maintain blood glucose by secreting insulin. This demands energy and resources to accomplish that. Many times, the same cells need to increase their numbers to meet the body's every changing demands. Like beta-cells multiple in cases of obesity. Cell division is also an energetically costly process. It has to make two of almost everything: two sets of DNA, two times the mitochrondria, before dividing into two. How does the cell balance the resources between its function and cell division processes?? 

Jonathan Coloff and colleagues asked the same and found that the answer does not lie in different starting material, but how the raw materials are processed. A cell's carbon demands can be satisfied by glucose, but nitrogen comes mostly from glutamate; which helps build nuclei acids, proteins and other machinery. Quiescent cells performing normal function process glutamate to ammonia vs. proliferative cells that would make non-essential amino acids from it. This difference in processing describes the switch between the two cellular states. To learn more about the switch, please listen to Jon.

To know more about the study, please refer to:

Differential Glutamate Metabolism in Proliferating and Quiescent Mammary Epithelial Cells
Jonathan L. Coloff et al., Cell Metabolism. May 2016.

Immunological Curate's Egg -- Interview with Chong Luo about defining the line between tumor elimination and autoimmunity.

Immune cells in our body not only function to ward off infections, but also eliminate unfit, and possibly cancerous cells. For this, T cells, a part of our adaptive immune response, recognize the harmful cells within the body and kill them. But sometimes they can get confused, and are unable to distinguish between harmful and normal cells. In this case, they start attacking functional organs, leading to auto-immune disorder. What helps them maintain the capacity to successfully make such distinctions??

Chong Luo and her colleagues probed this query and found that a transcription factor, Foxo1, helps define this fine line. Foxo1 expression level decreases in a certain class of Treg cells during their fight with tumor cells. However, continued expression of Foxo1 in such Treg cells impairs the response and shifts it towards autoimmunity. To understand such regulation, please listen to in to an interview with Chong.


To know more about the work, please read:
Graded Foxo1 activity in Treg cells differentiates tumour immunity from spontaneous autoimmunity
Luo et al., Nature, 2016.

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?

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.