Don't judge a book by its cover. Different neural circuitry underlying similar behavior by Akira Sakurai!

It is assumed that similar behaviors are generated by similar neuronal mechanisms. If nature has found one way of doing things, it will reuse it again and again for the same purpose. Akira and colleagues wanted to investigate this phenomena in the swimming behavior of two closely related molluscs. The swimming behavior of the two species is generated by very similar neurons, yet when they looked closely, the connections between neurons differed drastically. This suggested that the swimming behavior used the same same blueprint, but different architecture. To know more, please listen to Akira.  


For more information, please refer to:
Artificial Synaptic Rewiring Demonstrates that Distinct Neural Circuit Configurations Underlie Homologous Behaviors
Akira Sakurai and Paul S. Katz, Current Biology, June 2017

Blood from lungs! Interview with Emma Lefrançais on platelet production in lungs!

Blood nourishes every part of our body. It is generated every day to carry oxygen and food towards, and garbage away from every cell. Our lungs breathe in the oxygen that goes to the blood and remove carbon dioxide from it. Do lungs passively interact with circulating blood, or can they even generate new blood cells and spread them through the body?

Emma and colleagues wanted to test lungs as an active area of blood production. For this, they live imaged the blood cells within the lungs of mice. This amazing feat showed them platelets being born inside of the lung. And this pool of platelets were not a minority, but a significant part of blood count. Not only did they find platelet birth, but they also found blood stem cells living in the lung. These cells could, under certain conditions, help recover many types of blood cells! To know more about this exciting and profound discovery, please listen to Emma.


For more information, please refer to:
The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors
Lefrançais et al., Nature, 2017

It's an emergency! Interview with Gesa Zander on cellular response to heat stress!

Imagine a sudden crisis within a country. One day, suddenly, there is a need to face an impending disaster. What happens? The people go into panic-mode and stop doing their regular jobs, and instead focus on averting the crisis. Normal production ceases, and things needed to face the disaster are produced. The pace of production is ramped, and irrespective of the quality, a huge quantity of emergency supplies is generated.

Like humans, cells in our body also face crisis. They need to adapt to extreme environments quickly in order to survive and thrive. Gesa, Alexandra, Lysann and colleagues wanted to know what happens to the cellular production process during the stress period. How does the cell switch to producing cell-responsive genes. And not only producing, but producing at a fast-pace. Are the quality controls applicable during normal times also applicable during the frantic response to stress. They find that the cell switches to stress-control mode, and for a certain time, eases on the quality controls of production. Please listen to Gesa on the interesting adaptability of the cells.


For more information, please refer to:
mRNA quality control is bypassed for immediate export of stress-responsive transcripts
Zander et al., Nature, 2016

A Time to Spring! Interview with Julia Qüesta on cold sensation in plants!!

Winter ends and the layer of snow clears off the ground. The soil is fresh for new cycle of vegetation. It instantly converts to a beautiful expanse of flowers and fresh plants. How does such a drastic change occur? How did the plants 'know' the change in seasons. They don't have an almanac or the weather channel to tell them of the ending cold, or do they??

Julia and colleagues undertook to understand the sensing of winter-to-spring transformation in plants. It is possibly the most important decision for the survival of the plant. Arising anew from winter needs to be perfectly timed. A little early, and the frosty cold will chill the new life. A little late and the other plants would have taken away precious space and resources, making it difficult to fight for survival. And importantly, its a one time event: an on-off switch. The plant needs to integrate a million parameters into a single result. An elaborate chain of events culminating into a life or death choice.

How does the switch operate? Julia and colleagues map the system to basepair resolution by finding the machinery and its corresponding binding sites on the plant genome for controlling the process. This amazing feat (for plant and the team) is a perfect example of how simplicity underlies complex decision making. To understand more, please listen to Julia.



To know more, please refer to:
Arabidopsis transcriptional repressor VAL1 triggers Polycomb silencing at FLC during vernalization.
Qüesta et al., Science 2016.

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
  

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.  

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.

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.

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.

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. 

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

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.

Call with Arjun Raj

Today we call Dr Arjun Raj from UPenn to discuss cellular heterogeneity: how seemingly similar cells might be very different from each other if looked at closely. We also talk about scientific method and training; guidelines for scientist at any stage.

Please listen.

To learn more about Arjun Raj's work, visit his lab website.


Citations:
Stochastic mRNA synthesis in mammalian cells
Raj et al., PLoS Biol., October 2006.

Half dozen of one, six billion of the other: What can small- and large-scale molecular systems biology learn from one another?
Genome Research, October 2015.

Top 10 signs that a paper/field is bogus