The Complicated Immune Response: Annual Review of Immunology, Volume 35

Browse the Annual Review of Immunology, Volume 35 table of contents.

While proofing this volume, I was impressed again by how complicated the immune system is. It seemed so very simple in high school biology! But there are so many related actions that have to happen in precise sequences, and even systems that I thought were disconnected from immunity turn out to be quite important. For instance, see the abstract of “The Lymphatic System: Integral Roles in Immunity” by Gwendalyn Randolph et al.:IY35-lymphatic

The lymphatic vasculature is not considered a formal part of the immune system, but it is critical to immunity. One of its major roles is in the coordination of the trafficking of antigen and immune cells. However, other roles in immunity are emerging. Lymphatic endothelial cells, for example, directly present antigen or express factors that greatly influence the local environment.

The study of immunology has progressed in recent years and is producing huge amounts of data—as I discovered in Arup K. Chakraborty’s article, “A Perspective on the Role of Computational Models in Immunology.” To make use of that data, because the processes are so complex, researchers are using computational models:

Computational or theoretical studies of the model can keep track of every possible event that can occur consistent with a hypothesis and reveal whether a particular hypothesis is plausible. Hypotheses that appear feasible at first glance can be incorrect because of the complexity of the underlying phenomena. Computational biophysics–based models not only can screen out these hypotheses prior to fruitless experimental tests, but also can shed light on the reason a hypothesis is unlikely to be right and thus guide the choice of other feasible hypotheses. Such computational studies are not exercises in fitting parameters to quantitate known mechanistic models. Rather they offer ways to obtain mechanistic insights and guide the choice of meaningful hypotheses underlying puzzling observations and the design of realistic experiments that can test the hypotheses.

Another article that caught my interest was Kole T. Roybal &Wendell A. Lim’s “Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.” I was intrigued by the title’s use of “hacking” in a biomedical context and the article itself proved to be fascinating!

[I]mmune cells are relatively easy to remove, modify, and transfer back into a patient. Given these unique properties, immune cells provide a remarkable platform for interfacing with and treating disease. There are many complex diseases, such as cancer and autoimmunity, that our natural immune systems either cannot handle or pathologically contribute to. Thus, there is a strong rationale to engineer new disease sensing and response behaviors in immune cells, especially given recent powerful advances in synthetic biology and genome editing, which give us unprecedented ability to modify and engineer cellular functions.

Suzanne K. Moses is Annual Reviews’ Senior Electronic Content Coordinator. For 15+ years, she has played a central role in the publication of Annual Reviews’ online articles. Not a single page is posted online without first being proofed and quality checked by Suzanne.

 

Research partners: Happy Valentine’s Day from Annual Reviews

I have a soft spot for the Annual Review autobiographies. I open each volume’s table of contents and eagerly search for them. I’m always interested in how our authors discovered their passion for their field and the interplay between their lives and their science. Among these articles there are a few that are written by husband and wife teams—and they are an extraordinary glimpse into shared lives.

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I first encountered Leonard and Leonore Herzenberg in their article “Genetics, FACS, Immunology, and Redox: A Tale of Two Lives Intertwined,” published in the Annual Review of Immunology in 2004.  I was quite taken with the way they handed the narrative back and forth, as well as the humor with which they told their story. I was delighted to find them writing for us again in 2014 for the Annual Review of Physiology, and even more delighted to find they had done a video interview!  These two articles remain among my favorites, and I was sad to learn that Dr. Leonard Herzenberg had passed away soon after the video was made.

Here is a snippet from Dr. Leonore Herzenberg about their time in Paris at the Pasteur Institute from the 2004 volume of the Annual Review of Immunology:

…because Len loved hands-on experimentation, I took over much of the data recording, computation, and display (plotting) that was needed. The work was tedious (slide rules were the closest thing to computers at the time). However, it gave me the opportunity to do a preliminary analysis of the data and try novel approaches to analyzing LacZ induction kinetics. Len left this to me. He was more interested in developing methods and experiment designs that would enable clear conclusions without a lot of mathematical interference. This division of labor, which reflects Len’s innate preference for concreteness and my innate love for theory, remains with us even today.

bb-richardsonsDrs. Jane and David Richardson wrote “Doing Molecular Biophysics: Finding, Naming, and Picturing Signal Within Complexity” for the Annual Review of Biophysics in 2013. While the article focuses mainly on their research, it is full of stories about their shared experiences, such as this one:

We spent a large fraction of our lives from the early 1970s to the early 1990s in Fred Brooks’ computer graphics lab at the University of North Carolina (UNC). There we accomplished much of our own research in protein structure, acted as guinea pigs for in-depth testing of their software and hardware, and played happily with the science fiction–level gadgets that explored far-out new possibilities such as virtual reality displays, volume rendering, force feedback, fitting models into electron density, or tugging on atoms to move local structure with (more or less) physical realism. Some things worked splendidly and soon became widespread; some failed by being surprisingly unhelpful, making you sick, or whacking you in the chest (their gadgets never just fell apart)…

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In 1989, George and Eva Klein wrote “How One Thing Has Led to Another” for the Annual Review of Immunology.  Their story begins with a whirlwind romance and an intrigue-filled move into Sweden just as the Iron Curtain was falling on Dr. Klein’s Hungarian homeland.  From the epilogue of their article:

As each of us is moving towards the approaching darkness, the sun is never setting over the vast oceans of science. It has been a rare privilege to live and work through the times when the genetic material turned from protein to DNA, when adaptive changes in cell populations-including antibody production-were unmasked as Darwinian variations and selection, when GOD became the rearrangement of immunoglobulin genes, violating the dogma that all somatic cells have the same DNA….It was a great time, and it still is, but it is only the stumbling, stuttering, premature foreshadowing of what lies ahead. We have barely scratched the surface.

bi-taborThe story of Celia White Tabor and Herbert Tabor’s work in biochemical research was chronicled along with their personal history in the article “It All Started on a Streetcar in Boston” for the Annual Review of Biochemistry in 1999.  Among the scientific discussion are small stories about their lives and friendships, making this an interesting read.

We first met on a Boston streetcar in 1940, being introduced by a mutual friend. Celia was returning from research work at the Massachusetts General Hospital as part of her senior thesis at Radcliffe College, and Herb was returning from a concert by the Boston Symphony. We were married in 1946 after Celia had finished her medical training. We started working together in 1952, and we are still actively collaborating in our studies on various aspects of the biosynthesis and function of polyamines.

Suzanne K. Moses is Annual Reviews’ Senior Electronic Content Coordinator. For 15+ years, she has played a central role in the publication of Annual Reviews’ online articles. Not a single page is posted online without first being proofed and quality checked by Suzanne.

Runners-Up for Person of the Year: CRISPR Scientists

Time Magazine named U.S. President-Elect Donald Trump its 2016 Person of the Year, but amongst the runners-up are the scientists who identified the mechanisms and developed the technique of gene editing using clustered regularly interspaced short palindromic repeats (CRISPR), as well as those who are attempting to find direct applications in human health.

The implications are significant for the treatment of diseases with genetic components. If gene sequences can be altered, they can also be corrected to eliminate the risk of illnesses such as cystic fibrosis or Huntington’s Disease. They can also be used in the treatment of certain cancers. The technique is all the more revolutionary because it is cheap, very accurate, and easy to use.

While many of the scientists involved in these discoveries co-signed a letter urging caution in the use of CRISPR, wary as they are of genome modifications that could be passed on to offspring, this new technology also offers a lot of hope for many diseases that have not yet found a cure.

Jennifer Doudna, of the University of California at Berkeley, along with Emmanuelle Charpentier of the Max Planck Institute, developed a way to simplify this technology and apply it to all kinds of DNA. Feng Zhang, of the Massachusetts Institute of Technology, showed it was possible to use it on human DNA. Carl June, of the University of Pennsylvania, is now attempting to harness CRISPR to treat cancer.

Congratulations to all of them.

Browse Dr. Doudna’s articles for Annual Reviews:

2016 Lasker Awards

Congratulations to the winners of the 2016 Lasker awards.

1. Basic Medical Research Award:

William G. Kaelin, of Dana Farber-Harvard Cancer Center.

Gregg L. Semenza, of Johns Hopkins University.

They helped identify how all animals react to variations in oxygen. They share the award with Peter J. Ratcliffe, of Oxford University. Click on their names to read the articles they wrote for various Annual Reviews journals.

2. Lasker-DeBakey Clinical Medical Research Award:

Charles M. Rice, of Rockefeller University.

He shares the award with Ralf  F. W. Bartenschlager, of the University of Heidelberg, and Michael J. Sofia, of Arbutus Biopharma. Drs. Rice and Bartenschlager were able to find a way to make the Hepatitis C virus replicate in laboratory conditions, which allowed research to proceed. Dr. Sofia then developed a drug that made it possible to treat the disease.  Click on Dr. Rice’s name to browse the articles he wrote for various Annual Reviews journals.

3. Lasker-Koshland Award for Special Achievement in Medical Science:

Bruce M. Alberts, of the University of California, San Francisco.

He was recognized for his work in molecular biology and his efforts toward science education. Click on his name to browse the articles he wrote for the Annual Review of Biochemistry.

Our Microbial Partners

Congratulations to Ed Yong on his new book, I Contain Multitudes: The Microbes Within Us and a Grander View of Life, in which he explores the microbes that live and multiply all over humans and other animals, helping us thrive and shaping our behavior.

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While our view of microbes is still heavily skewed by the germ theory of disease, which paints them solely as pathogens, recent research has shown that an estimated 50% of the cells we carry around are microbial in nature, and only a fraction of these actually make us ill.

In fact, each animal is an ecosystem and our individual microbiomes play an essential role in keeping us healthy. They help us evolve, break down nutrients from the food we eat so we can better assimilate them, teach our immune system how to defend us from disease, and favor brain development, among other things. Scientists even found that germ-free mice exhibited autism-like behavior, and that probiotic therapies can have positive effects on depression and anxiety.

Yong cited seven of our articles in his book, all of which you can access for free for the next 30 days

The Influence of Milk Oligosaccharides on Microbiota of Infants: Opportunities for FormulasAnnual Review of Food Science and Technology
Biofilms and Marine Invertebrate Larvae: What Bacteria Produce That Larvae Use to Choose Settlement SitesAnnual Review of Marine Science
The Microbiome in Infectious Disease and InflammationAnnual Review of Immunology
Ecological Physiology of Diet and Digestive SystemsAnnual Review of Physiology
Vaginal Microbiome: Rethinking Health and DiseaseAnnual Review of Microbiology
Human Milk Glycans Protect Infants Against Enteric PathogensAnnual Review of Nutrition
The Human Gut Microbiome: Ecology and Recent Evolutionary ChangeAnnual Review of Microbiology

For more, listen to Yong discussing his book with Fresh Air‘s Terry Gross on August 18, 2016.