Metabolism and the evolution of social behavior

Kerry Boyle’s PhD paper is out today. It’s still in the early-view, unformatted version but it is now officially published!

In this paper we addressed a fundamental question: Why do organisms of many species seem to change their behavior toward others depending on their internal metabolic state? To investigate this problem at an ultimate level we carried experiments with swarming Pseudomonas aeruginosa, a bacterial model of social behavior. Experiments with bacteria allowed us to alter the metabolic state genetically and to determine—with a level of detail that would be difficult in more complex model organisms—how those changes influenced the evolution of social social behavior.

Our paper uses a combination of experimental evolution, molecular microbiology, whole-genome sequencing and is—to the best of our knowledge—the first to use metabolomics to investigate the role of metabolism in the evolution of a social behavior. This was only possible thanks to our collaborators at Kyu Rhee‘s lab, experts in microbial metabolomics.

metabolism_and_social_behavior

The implications go beyond P. aeruginosa: Natural selection favors organisms that can regulate their social behaviors and reduce their fitness cost-to-benefit ratio. Metabolism—currency of all physiological processes—is a very obvious away that social genes have to modulate the cost of a behavior; metabolism should influence social behavior in all organisms, including ourselves. For a review on genes and social behavior see Robinson et al, 2008, Science.

Metabolism and the evolution of social behavior
Kerry E. Boyle, Hilary T. Monaco, Maxime Deforet, Jinyuan Yan, Zhe Wang, Kyu Rhee and Joao Xavier. Molecular Biology and Evolution
[Open Access]

Watch a video abstract made by Natalie Anselmi:

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NYC BIG 2017

A conference that used to be a meeting for Bacillus researchers in the Northeastern United States and has broadened to other bacteria as well. This year the NYC/BIG is on June 8th. Hilary Monaco and Jinyuan Yan will talk about their work on Pseudomonas aeruginosa. See:

http://www.nyu.edu/as/biology/events/nybig2017/

nybig2017

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Cancer metabolites organize the tumor microenvironment

Cancer cells are not alone: As cancerous tumors grow unregulated cancer cells engage other cells, in their path of destruction like macrophages which are part of the immune system and endothelial cells which make blood vessels. This collection of non-cancer cells that powers cancer growth is called the tumor microenvironment. How does the tumor microenvironment help cancer cells proliferate even more?

Answering this question is a holy grail of cancer science and holds the key to new therapies. Cancer cells, with their many mutations and unchecked DNA damage, change constantly: they can be a moving target for therapy and develop resistance to drugs that seemed to work at first. The non-cancer cells in the tumor microenvironment are genetically stable. If we knew how these cells interact we could to stop the tumor microenvironment from feeding the cancer, halt cancer growth or even reverse it. On February 28 a team of SKI scientists published a significant advance. The answer—surprisingly—is in metabolism.

All cells rely on metabolism, the engine-like process that requires constant fuel and oxygen to run. Cancer cells have altered metabolisms: they consume lots of oxygen and dump metabolic waste such as lactic acid. Because of this, cancerous tumors should only grow so large before the toxic effects accumulate like pollution in a jam-packed city, and eventually slow cancer growth. This is prevented, however, by tumor-associated macrophages (TAMs) that respond to the harsh environment and start a tissue-repair mechanism to clean it up.

The SKI team started by observing the behaviors of TAMs in a mouse model of cancer. Then, they fabricated tissue-mimetic systems to recreate the same process in vitro. Using this approach they discovered that TAMs respond to low oxygen and to the presence of lactic acid and start producing a vascular endothelial growth factor (VEGF). This growth factor commands endothelial cells to start producing blood vessels—called neo-angiogenesis—a process that can bring new blood to struggling cancer cells, replenishing oxygen and removing toxic waste.

The tissue-repair response of macrophages is normally a good thing: it is how our body heals wounds and clears out toxic waste from muscles after intense exercise. In cancers, however, it can make cells with complementary skills—cancer cells, TAMs and endothelial cells—work together in a terrible way. Rescuing cancer cells from dying because of their own altered metabolism boosts the cancer to grow even more.

The SKI study established a new role for cancer metabolism in the interactions between cancer cells and their microenvironment. These findings lay the foundations for our understanding of cancer development, diagnosis and treatment.

But the study also showed how an interacting team of multidisciplinary scientists could answer a difficult cancer question: Craig Thompson brought his expertise in cancer metabolism, Johanna Joyce her expertise in the tumor microenvironment, and João Xavier his expertise in cancer systems biology, a new field that aims to integrate cancer concepts. Cancers subvert cells with complementary features in their path to destruction; figuring out its complex mechanisms—and new ways to fight them—may require teams of scientist with complementary skills.

The study was spearheaded by Carlos Carmona Fontaine, former postdoctoral researcher at MSKCC who is now assistant professor of Biology at the New York University.

Metabolic origins of spatial organization in the tumor microenvironment
Carlos Carmona-Fontaine, Maxime Deforet, Leila Akkari, Craig B. Thompson, Johanna A. Joyce, Joao B. Xavier. PNAS
[Open Access]

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2016 lab mug

mug2016Carlos Carmona Fontaine, in between finishing his paper and starting his lab at NYU, found time to make the official 2016 Xavier Lab MUG.

Colored in the beautiful parula map, the 2016 mug is the best mug in the world for coffee or tea.

Check out Carlos’s lab website carmofon.org. Join his new lab at NYU Biology and you might make it in time for the first-ever Carmona Fontaine Official Mug.

Read more about the 2016 lab mug and our other mugs in our paraphernalia page.

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NY/B.I.G. meeting

This Friday 10:00am – 6:15pm at NYU
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Kerry Boyle talks about “The metabolomic basis of social behavior” at 10:20-10:35.
More about it: http://biology.as.nyu.edu/object/biology.events.nybig2016

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High school students and teachers at MSK for the 2015 “Major Trends in Modern Cancer Research”

On Tuesday, November 10, MSK hosted the tenth annual “Major Trends in Modern Cancer Research” lecture for high school and college students. The session was moderated by Craig Thompsons and featured Kat Hadjantonakis, Cole Hanes and me. The whole session is on youtube.

High school students at MSK for the 2015

High school students at MSK for the 2015 “Major Trends in Modern Cancer Research”

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Journal covers

During my PhD, 1999-2003, most scientific articles I needed for my research where only available in print. I’d go down to the library and take hours photocopying articles from piles of journals.
I also listened to a lot of CDs and I loved the cover art. I haven’t picked up a CD in a while and I’m pretty sure new CDs are still made, but I don’t know who buys them. The art from new covers goes unnoticed – I haven’t seen one from the last 5 years or more.
Journals still get printed too, but like songs we get the articles online. Grad students don’t spend hours copying in the library, which is great. But some nice covers will go unnoticed.

Covers from the October 15 issue of Cancer Research (collaboration with Richard White's lab) and the December 2015 about issue of Applied and Environmental Microbiology (collaboration with Lars Dietrich's lab and Soren Sorens's lab).

Covers from the October 15 issue of Cancer Research (collaboration with Richard White’s lab) and the December 2015 issue of Applied and Environmental Microbiology (collaboration with Lars Dietrich’s lab and Soren Sorensen’s lab).

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