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Ancient Part of Immune System May Underpin Severe COVID

One of the immune system’s oldest branches, called complement, may be influencing the severity of COVID disease, according to a new study from Drs. Sagi Shapira and Nicholas Tatonetti at the Department of Systems Biology.

Drs. Sagi Shapira (right) and Nick Tatonetti
Drs. Nicholas Tatonetti (left) and Sagi Shapira

Among other findings linking complement to COVID, the researchers found that people with age-related macular degeneration—a disorder caused by overactive complement—are at greater risk of developing severe complications and dying from COVID.

The connection with complement suggests that existing drugs that inhibit the complement system could help treat patients with severe COVID-19.

The study was published in Nature Medicine . For the full article , visit the Columbia University Irving Medical Center Newsroom. 

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Wang Lab Work on Bioeconomics Featured in Wall Street Journal

Economic Markets and Biological Markets

In a similar manner to the ways in which countries make and trade goods, microbial cells within bacterial communities exchange metabolites to promote cell growth. This perspective could provide a way of studying microbial communities from the perspective of economics.

An article in the Wall Street Journal reports on a recent collaboration involving Columbia University Department of Systems Biology Assistant Professor Harris Wang and Claremont Graduate University economist Joshua Tasoff that identified some intriguing similarities between economic markets and the exchange of resources among microbes within bacterial communities. 

In an unusual marriage, biology and economics appear to be a match made in heaven.

Four years ago, two former roommates reunited at a friend’s wedding had time to catch up. The first, an economist, asked: “What are you working on?” The second, a biologist, answered: “How microbial communities interact. It’s kind of like in economics.”

And that’s when the intellectual sparks began to fly.

Turns out microbial communities—what most of us think of as germs—expand by trading metabolites such as amino acids with other species of bacteria, just like free-market economies grow by exchanging goods and services.

That novel insight, inspired by a chance conversation and supported with research developed over the intervening years, provides a framework to explain how different species of bacteria interact in complex communities.

You can read the entire article here: Economies of Ail: How Bacteria Flourish. [login may be required]

Related publication

Tasoff J, Mee MT, Wang HH. An economic framework of microbial trade. PLoS One. 2015 Jul 29;10(7):e0132907.

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Kyle Allison Featured in NIH Director’s Blog

Kyle AllisonKyle Allison, a Systems Biology Fellow in the Columbia University Department of Systems Biology and recent winner of a National Institutes of Health Early Independence Award, is featured this week in a blog post authored by NIH Director Francis Collins. The article highlights Dr. Allison’s ongoing efforts to use approaches based in systems biology to understand bacterial persistence, a phenomenon that in clinical settings can often lead to dangerous, difficult-to-manage infections.

Read the complete post here: Creative Minds: Searching for Solutions to Chronic Infection.

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Harris Wang Named Office of Naval Research Young Investigator

Gut-Brain Microbiota
A grant from the Office of Naval Research will support the development of three foundational synthetic biology technologies for engineering the human gut microbiota.

Harris Wang, an assistant professor in the Columbia University Department of Systems Biology, has been selected for the Office of Naval Research 2015 Young Investigators Program. This highly selective program promotes the development of early-career academic scientists whose research shows exceptional promise and creativity. With the support of this award, Dr. Wang will extend his research in the field of synthetic biology to develop new technologies for engineering the gut microbiome, the ecosystem of bacteria that inhabit the human digestive system. These new methods, Wang anticipates, could provide new ways of designing communities of different microbial species and ultimately modulating interactions between the gut, the immune system, and the brain.

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Functional Metagenomics Enables First Study of Bacterial Fitness in the Gut Microbiome

Gut bacteria

Photo by David Gregory and Debbie Marshall, Wellcome Images. 

Recent deep sequencing studies are providing an increasingly detailed picture of the genetic composition of the human microbiome, the diverse collection of bacterial species that inhabit the gut. At the same time, however, little is known about the dynamics of these colonies, particularly why certain microbial strains outcompete others in the same environment. In a new paper published in the journal Molecular Systems Biology, Department of Systems Biology Assistant Professor Harris Wang, in collaboration with Georg Gerber and researchers at Harvard University, report on their development of the first method for using functional metagenomics to identify genes within commensal bacterial genomes that give them an evolutionary fitness advantage.

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Tracing Bacterial Evolution Across Billions of Years

Bacterial evolutionary relationships

Image courtesy of Germán Plata and Dennis Vitkup.

Columbia News has just published an article covering recent research by associate professor Dennis Vitkup and postdoctoral research scientist Germán Plata that uses simulations of bacterial metabolism as a lens for studying how phenotypes adapt and diversify across evolutionary time scales. The article reports:

Despite their omnipresence, microbial evolutionary adaptations are often challenging to study, partly due to the difficulty of growing diverse bacteria in the lab. “Probably less than a dozen bacteria are really well studied in the laboratory,” Vitkup says.

Writing in the journal Nature this past January, Vitkup and Plata applied computational tools to investigate bacterial evolutionary adaptations by simulating metabolism for more than 300 bacterial species, covering the entire microbial tree of life.

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Harris Wang Named Winner of Sloan Research Fellowship

Harris Wang

Harris Wang, an assistant professor in the Columbia University Department of Systems Biology and Department of Pathology and Cell Biology, has been selected to receive a 2015 Alfred P. Sloan Foundation Research Fellowship in computational and evolutionary molecular biology. This two-year, $50,000 grant will support work that combines methods from synthetic biology and computational biology to study how horizontal gene transfer contributes to microbial evolution.

Since 1955, the Sloan Research Fellowship program has supported outstanding early-career scientists in recognition of their achievements and their potential to make important contribution to their fields. This year’s fellows included 126 investigators, with 12 awardees in the field of computational and evolutionary molecular biology. Other disciplines represented in the awards include chemistry, computer science, economics, mathematics, neuroscience, ocean sciences, and physics.

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Prestigious NIH Director's Awards Go to Two Department of Systems Biology Researchers

Dana Pe'er and Kyle Allison

Dana Pe'er has received the Pioneer Award for high-risk, high-reward research, and postdoctoral scientist Kyle Allison has won an Early Independence Award.

Two members of the Columbia University Department of Systems Biology have been named recipients of NIH Director’s Awards from the National Institutes of Health Common Fund.

Associate Professor Dana Pe’er is one of 10 winners of the 2014 NIH Director’s Pioneer Awards. The Pioneer Awards provide up to $2.5 million over 5 years to support exceptionally creative investigators who are pursuing “high risk, high reward” science that holds great potential to transform biomedical or behavioral research. The award will support an ambitious new project to develop the technological and computational methods necessary to create a comprehensive, high-resolution atlas of development for all cell types in the human body.

In addition, Kyle Allison, a postdoctoral scientist in the laboratory of Professor Saeed Tavazoie, has received the NIH Director’s Early Independence Award. (Dr. Tavazoie is also a past winner of the Pioneer Award.) This program enables outstanding young investigators who have recently completed their PhD’s to move rapidly into independent research positions. Dr. Allison is one of just 17 scientists to receive this award this year. In combination with the Department of Systems Biology Fellows program, this five-year, $1.25 million grant will allow him to open his own laboratory at Columbia and pursue independent research to investigate the problem of bacterial persistence. He is the second Department of Systems Biology investigator to receive the Early Independence Award, joining Assistant Professor Harris Wang in being recognized with this honor.

“Having four recipients of NIH Director’s Awards within the Department of Systems Biology — and particularly two in one year — is quite remarkable,” said Department Chair Andrea Califano. “I think it’s a testimony to the timeliness of the perspectives and tools that systems biology offers and to the high quality of research being conducted at Columbia. I look forward to the discoveries that will undoubtedly come from Dana’s and Kyle’s extremely exciting efforts.”

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Grant Will Support Annotation of Metabolic Networks in Pathogenic Bacteria

M. Tuberculosis Culture

M. tuberculosis bacterial colonies. Photo credit: CDC/Dr. George Kubica [Public domain], via Wikimedia Commons

Dennis Vitkup, an associate professor in the Columbia University Department of Systems Biology and Department of Biomedical Informatics, has  been awarded an R01 grant from the National Institute of General Medical Sciences (NIGMS) to develop a computational pipeline for predicting bacterial metabolic networks. Building on a framework called GLOBUS that was previously developed in his lab, the project will produce probabilistic annotations of metabolic networks for all of the major bacterial species that cause disease in humans. It will both offer a method that can be used to study metabolism in any species of bacteria and produce valuable information that will aid researchers who are looking for therapies against many of the world’s most deadly pathogens.

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Systems Biology Throws You Out of the Box: An Interview with Saeed Tavazoie

Saeed Tavazoie

One of the defining features of systems biology has been its integration of computational and experimental methods for probing networks of molecular interactions. The research of Saeed Tavazoie, a professor in the Columbia University Department of Systems Biology, has been emblematic of this approach. After undergraduate studies in physics, he became fascinated by the processes that govern gene expression, particularly in understanding how gene expression is regulated by information encoded in the genome. Since then, his multidisciplinary approach to research has generated important insights into the principles that orchestrate genome regulation, as well as a number of novel algorithms and technologies for exploring this complex landscape.

In this conversation, Dr. Tavazoie discusses his research in the areas of gene transcription, post-transcriptional regulation, and molecular evolution, as well as some innovative technologies and experimental methods his lab has developed.

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A Topological Approach to Modeling Evolution

Models of Evolution In Charles Darwin's seminal treatise On the Origin of Species there is only one image, which visualizes evolution as following a branching pattern in which species diverge into lineages over time like the limbs on a tree. With the increasing availability of genomic data, scientists have attempted to understand evolution at the molecular level by using a similar phylogenetic paradigm, but as Department of Systems Biology Assistant Professor Raul Rabadan , MD/PhD student Joseph Chan, and Stanford University mathematician Gunnar Carlsson point out in a new paper published in the Proceedings of the National Academy of Sciences , it has a number of shortcomings when applied in this way. By developing a new mathematical approach based on a method called persistent homology, the researchers produced several insights into viral evolution that could not be found using other means.

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A First Method for Global Probabilistic Annotations of Metabolic Networks

GLOBUS algorithm

 An overview of the GLOBUS algorithm.

A Columbia University team led by professor Dennis Vitkup and PhD student German Plata of the Center for Computational Biology and Bioinformatics has developed a novel genome-wide framework for making probabilistic annotations of metabolic networks. Their approach, called Global Biochemical Reconstruction Using Sampling (GLOBUS), combines information about sequence homology with context-specific information including phylogeny, gene clustering, and mRNA co-expression to predict the probability of biochemical interactions between specific genes. By integrating these different categories of information using a principled probabilistic framework, this approach overcomes limitations of considering only one functional category or one gene at a time, providing a global and accurate prediction of metabolic networks.

In a paper published in Nature Chemical Biology, the scientists write, "Currently, most publicly available biochemical databases do not provide quantitative probabilities or confidence measures for existing annotations. This makes it hard for the users of these valuable resources to distinguish between confident assignments and mere guesses... The GLOBUS approach, which is based on statistical sampling of possible biochemical assignments, provides a principled framework for such global probabilistic annotations. The method assigns annotation probabilities to each gene and suggests likely alternative functions."

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Tracking the H1N1 Pandemic Virus

Flu cases in early 2009

Because flu viruses mutate nearly once every reproduction cycle, no two people are made sick by precisely the same virus, as illustrated by this chart documenting swine flu cases among humans in early 2009.

The recent outbreak and sudden spread of a novel H1N1 influenza virus has caused a worldwide concern and has tested our ability to respond to major public health challenges. Significant scientific resources have been marshaled to discover the best possible responses against this novel swine origin influenza virus. A group led by Raul Rabadan at the Center for Computational Biology and Bioinformatics, and the Department of Biomedical Informatics at Columbia University has been studying the evolution of influenza viruses and the origins of flu pandemics by analyzing large data sets that contain genomic information.

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