Another “before and after” text from a new science writer

Jon Paul Hildahl, a postdoctoral researcher at the University of Oslo, wanted to try some popular science writing and produced this text. We worked on it a bit together and then he revised it. Here are the “before” and “after” versions. I’ll provide some commentary in the next post. The main issues were editing – removing redundant or unnecessary language, unraveling a bit of the science, and providing illuminating explanations for a more general audience. Thanks for providing this, Jon – you truly have a future as a science writer (alongside your own excellent research, of course). Jon currently works in the group of Gareth Griffiths at the University of Oslo, where I conduct a week-long course every December for Masters’ students. It’s always one of the highlights of my year. Thanks to Jon for letting me post this, with his name.

BEFORE:

Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development
Jorge Galindo-Villegas et al 2012 PNAS

It is obvious that we are not alone in this world, but it is becoming increasingly clear that we are not even alone in our own bodies. We are covered inside and out by small critters called microbes that include many helpful bacteria, archaea and fungi, collectively called commensals. The resident population that we carry throughout much of our life is called our microbiome. It is very abundant; our body contains 10 times as many microbial cells as human cells. It is not surprising then that these cohabitants play an important role in human health. Indeed their effect on animal health is an area of active research. In particular, it is becoming clear that a little dirt is good for you, especially in your early formative years. It has been shown in multiple animal models that microbes in the environment during early development can help establish the immune system and protect the host from attack by disease causing bacteria. This study helps to clarify the mechanisms by which this initial microbial exposure is controlled at the cellular and genetic level using a powerful fish model.

These researchers have used two powerful models to delineate the role of commensal bacteria during development of the immune system: 1.) germ free condition in 2.) the zebrafish model. Many studies of the role of environmental bacteria use germ free models. This provides a reference to what would happen in the absence of resident microbes. This can then be compared to the natural situation of exposure and colonization by commensals. Fish are exposed to a rich microbial ecosystem in their aquatic environment, which suggests that they have evolved ways to deal with environmental microbes both good and bad. You might ask, however, what a fish can tell us about human biology? Luckily, many if not most developmental processes are conserved among distantly related animal groups. Additionally, the zebrafish have many advantages as a research animal since they develop quickly in transparent eggs that can be easily followed and manipulated. They also have a well-characterized genome and sophisticated genetic tools that allow researchers to add or subtract gene products and measure the level of gene expression. It is known that the initial and fast acting (also called innate) immune system develops within days and before hatching for zebrafish.

In this study, the authors were able to follow the immune response of zebrafish from the time they hatch, at around two days after fertilization, and for the first days of exposure to the external environment when commensal colonization is believed to occur. They showed that zebrafish have a rapid and punctuated innate immune response after hatching, peaking after one day and then decreasing. This initial activity improves the response of early immune cells, providing a better protection against pathogenic bacterial infection and tissue damage compared to fish reared in germ free conditions. The researchers were also able to show that innate immune cells respond by a conserved mechanism, involving a intracellular response pathway by the myeloid differentiation primary response protein 88, MyD88. Another important finding from this study is that epigenetic regulation, which modifies the ability of genes to be expressed, modifies the immune response such that a robust emergency response is in place in case of infection or injury, while reducing the risk of adverse immune effects due to excessive inflammation by providing initial responders (antimicrobial effector proteins) that are not limited by epigenetic regulation.

AFTER:

The ying and yang of germ warfare

None of us go through life alone – not even within our own bodies. We are covered inside and out by microbes that include many helpful bacteria, archaea and fungi, collectively called commensals. The resident population that we carry throughout much of our life is called our microbiome. It is very abundant; each body contains 10 times as many microbial cells as human cells. It is not surprising then that these cohabitants play an important role in human health, an area of active research. One of the results is to show that a little “dirt” is good for you, especially in your early formative years. Studies using several animal models show that during early development, environmental microbes help establish the immune system and protect the host from disease-causing bacteria. A recent paper entitled, “Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development” uses a powerful fish model to provide new insights into the mechanisms by which this early microbial exposure mediates cellular and genetic responses.

Jorge Galindo-Villegas and colleagues at the University of Murcia in Spain have compared zebrafish in two settings to clarify the role of commensal bacteria during immune system development: fish raised in a normal environment, and those raised in germ-free conditions. Germ-free models are commonly used to simulate what might happen in the absence of resident microbes, compared to the natural situation of exposure and colonization by commensals. Fish are normally exposed to a rich microbial ecosystem in their aquatic environment, which suggests that they have evolved ways to deal with environmental microbes that have both good and bad effects.

What, you may ask, can a fish tell us about human biology? Luckily, most significant developmental processes are conserved among distantly related animal groups. And zebrafish have many advantages as a research animal: They develop quickly in transparent eggs that can be easily observed and manipulated. Their well-characterized genome and sophisticated genetic tools allow researchers to add or subtract molecules and measure how genes – including the components of the immune system – respond. Another advantage is that the initial, fast-acting (“innate”) part of the immune system develops within days – even before zebrafish hatch.

The authors of this study followed the immune response of zebrafish from the time they hatch (at around two days after fertilization) through the first days of exposure to the external environment, when most commensal colonization is believed to occur. They showed that zebrafish have a rapid and punctuated innate immune response after hatching, which peaks after one day and then decreases. This initial activity improves the response of early immune cells, providing better protection against later pathogenic bacterial infections and tissue damage than is observed in fish reared in germ-free conditions. The researchers also showed that innate immune cells respond to these early infections using a mechanism that is found in many other animals, including humans. The response activates a biochemical signaling pathway in cells involving the myeloid differentiation primary response protein 88, or MyD88, which helps recognize microbes and initiate a immune response.

Another important finding from the study is that during early development, factors that influence the way DNA is packaged alter the patterns by which genes typically respond to stimuli. While fish that are exposed possess the same genes as fish that are not, early infections and environmental conditions cause their cells to establish patterns in which certain genes become active and others remain silent. The effect of this type of “epigenetic” regulation is to provide an extra level of control, giving cells the ability to mount a robust emergency response in case of infection or injury, but without the adverse immune effects – which can happen when inflammation reaches a serious level. Even fish raised under germ-free conditions mounted a slight immune response by this means. In contrast, antimicrobial effector proteins, which provide the fish with a fast-acting initial response system, have sustained high expression that is not limited by epigenetic regulation. Altogether, this study nicely demonstrates how commensal bacteria are closely intertwined with the development of the their host’s immune system.

Author: Jon Paul Hildahl
Link to the free full text of the original article

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