Researchers have developed a new informatics technology that analyzes existing data repositories of protein modifications and 3D protein structures to help scientists identify and target research on “hotspots” most likely to be important for biological function.
Known as SAPH-ire (Structural Analysis of PTM Hotspots), the tool could accelerate the search for potential new drug targets on protein structures, and lead to a better understanding of how proteins communicate with one another inside cells. SAPH-ire has been tested on a well studied class of proteins involved in cellular communication, where it correctly predicted a previously-unknown regulatory element.
“SAPH-ire predicts positions on proteins that are likely to be important for biological function based on how many times those parts of the proteins have been found in a chemically-modified state when they are taken out of a cell,” explained Matthew Torres, an assistant professor in the School of Biology at the Georgia Institute of Technology. “SAPH-ire is a tool for discovery, and we think it will lead to a new understanding of how proteins are connected in cells.”
The tool and its proof-of-concept testing were reported June 12 in the journal Molecular and Cellular Proteomics. The research was supported by the National Institutes of Health’s National Institute of General Medical Sciences (NIGMS) and Georgia Tech.
Through modern mass spectrometry proteomics techniques, scientists have identified more than 300,000 post-translational modifications (PTMs) in different families of proteins across numerous species. These PTMs come in many forms, resulting from the action of different enzymes, and are often indicators of how and where proteins contact one another to bring about different cell behaviors. The number of PTMs detected by mass spectrometry has grown so rapidly that researchers experimentally investigating the function of the modifications have been unable to keep up.
“Mass spectrometry is so effective that it has created an exponential curve in the knowledge of how proteins are modified,” said Torres. “The rate at which we can detect new PTMs has now far surpassed the rate at which we can understand what they do, from a classical biochemical approach. You have so much information that you don’t know where to begin.”
But that’s exactly where SAPH-ire begins. Aimed at bridging the gap between PTM detection and analysis of function, SAPH-ire collects non-redundant and experimentally verified PTM data across all known members of a protein family. Since members of a protein family share the same or similar protein structures, PTMs found within the family can be related to one another in three-dimensional space to produce a set of observed PTM frequencies, termed “hotspots.”
The PTM hotspots are projected onto 3D protein structures available in the Protein Data Bank (PDB), which allows the entire set of family-specific PTMs to be visualized on any protein structure that is representative for the family. Once projected there, SAPH-ire integrates multiple quantitative features from each hotspot to create a PTM “Functional Potential Score.” Each PTM hotspot can then be ranked in order of highest to lowest potential for having significant biological function.
“We have gone through all of what might be considered the meta-data that exists in the public domain, collected all the PTMs and all the structures, then organized them into their specific protein families,” Torres explained. “We are looking at PTMs through time, in a sense, because we have information from organisms that are evolutionarily distant from each other, though their proteins are related as members of a protein family.”
To prioritize research with the most significant potential impact, scientists might examine PTM hotspots that SAPH-ire identifies as having high function potential, but no known function.
Torres’ lab has been investigating unique families of “G” proteins, some of which cooperate with cell surface receptors that control the binding of hormones and neurotransmitters, as well as a majority of pharmaceutical drugs. Because of their importance to therapeutics, these proteins have been extensively studied over a period of 50 years or so. Using SAPH-ire, the researchers discovered something surprising about this group of protein families.
“We discovered a new regulatory element within a specific G protein family that has been largely ignored because it’s pretty unimpressive from a purely structural viewpoint,” Torres said. “SAPH-ire predicted that this element was going to be important from a modification point of view, and we confirmed experimentally that it was.”
SAPH-ire was conceived by Torres and developed by him and graduate student Henry Dewhurst, while experimental validation of the tool was accomplished by graduate student Shilpa Choudhury. Their next step is to develop collaborations with scientists who will try it out on the protein families they study. The Georgia Tech researchers are also creating a database that other protein scientists can query to help them identify and prioritize PTM hotspots, and they expect to see their program become part of informatics systems used to analyze large volumes of proteomics data emerging from labs around the world.
“SAPH-ire will help bring meaning and context to all the data that is being produced about PTMs,” Torres said. “Connecting SAPH-ire to other programs that convert mass spec data into actual PTM data could provide immediate biological relevance and prioritization for biochemists and others. It is likely to expose many new and unsuspected relationships between protein modification, protein structure and function.”
This research was supported by the National Institutes of Health, National Institute of General Medical Sciences (NIGMS), under grant number 5R00 GM094533-05. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
CITATION: Henry M. Dewhurst, Shilpa Choudhury and Matthew P. Torres, “Structural Analysis of PTM Hotspots (SAPH-ire) – a Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families,” (Molecular and Cellular Proteomics, 2015). http://dx.doi.org/10.1074/mcp.M115.051177
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The Gordon and Betty Moore Foundation and Research Corporation for Science Advancement awarded 5 grants totaling $731k to teams of researchers pursuing "ambitious, high-risk, highly impactful discovery research on untested ideas in physical cell biology."
One of the winning teams—composed of Brian Hammer (Georgia Tech), Raghuveer Parthasarathy (University of Oregon) and Joao Xavier (Memorial Sloan-Kettering Cancer Center)—proposed a long term project titled, “Rebooting the Gut Microbial Ecosystem using Bacterial Dueling”.
Studies abound linking particular diseases, such as Crohn’s, to the bacteria in our gut. Their project aims to demonstrate that bacterial dueling can be used to eliminate harmful bacteria in the gut and repopulate it with healthy bacteria.
To begin, the researchers will introduce vibrio cholerae into a sample of zebrafish. V. cholera is an aggressive bacterium that feeds on chitin, a complex carbohydrate and major component of exoskeletons. Zebrafish, a common sight in home aquariums, is an excellent model organism that also happens to have a taste for chitin-rich zooplankton.
When chitin is ingested, some of the sugars are released and sensed by V. cholera, which turns on its dueling machinery.
“What this means is that the response to chitin results in the production of a special protein factor (a transcription factor) in each Vibrio cholerae cell that can turn on the dueling machinery,” Dr. Hammer explained. “We can also genetically engineer Vibrio cholerae cells so that this special factor is always produced. These cells do not need chitin to activate dueling; it's on all the time.” Woe unto any microbe squatting alongside V. cholerae.
Interestingly, some strains of V. cholerae are especially bellicose, keeping their dueling machinery armed at all times, no chitin required.
Using fluorescent microscopy, the scientists will observe and subsequently model V. cholerae’s behavior under various conditions—by using different strains of V. cholerae (those that need chitin and those that are always battle-ready) and by manipulating the presence of chitin and other food sources.
For this research to ever have therapeutic applications, V. cholerae must be kept from running amok. Accordingly, the team plans to design a strain of V. cholerae with an off-switch. Hammer elaborated, “Basically, we engineer the cells so that they can only grow if provided an essential factor (a chemical we can add) for their cell wall. If we add that chemical to flasks of cells in the lab, and presumably into the water with the fish, the Vibrios grow normally. To make the cells self-destruct we simply remove that chemical from the water or move the fish into new water lacking that chemical.”
The last step in this study will be to repopulate the zebrafish’s gut with microbes found in healthy zebrafish.
If successful it “would suggest that we can develop dueling bacteria that could be used in humans to replace harmful bacteria in the gut with healthy ones… Finally, what I think is also really cool about our study is that [by manipulating chitin in the fish’s diet] it may also link the food we eat to how gut microbes interact,” beamed Hammer.
In August, Biology assistant professor Patrick McGrath was awarded a 5 year, $1.47 million grant by the National Institutes of Health to study the genetic architecture of aging. Most common diseases have a strong but complex genetic component. Understanding their genetic underpinnings will allow for their predictions and suggest targets for their amelioration. McGrath and colleagues will identify how age and epistasis affect traits in model organisms with the goal of identifying principles that can be applied to better predict the genetic variants responsible for human diseases.
A complex mixture of common and rare variants typically shape most biological traits – their exact effects mediated by extensive genetic interactions and organismal age. These observations are mainly correlative as little is known about the mechanisms that generate epistasis and age-dependence. Improved understanding of these processes could identify principles useful for predicting how causal factors act in novel genetic backgrounds and therapeutic techniques to take advantage of their non-linear effects to ameliorate disease. The broad objective of the proposed research is the identification of causative genetic variants affecting reproduction in the round worm C. elegans with age-dependent effect sizes and epistatic interactions. McGrath intends to mechanistically dissect their causes in the context of organ and multicellular circuit function. His team will study how life history changes in sperm number, a limited resource necessary for reproduction, creates age-dependent genetic architecture. Finally, they will study how epistasis and aging are shaped by the function of the underlying neural circuits responsible for the regulation of reproduction. These experiments will leverage C. elegans tractability to identify principles relevant to the study of human diseases.
In August, Biology Professor Yury Chernoff was awarded a 3 year NSF Molecular and Cellular Biology grant to investigate the control of heritable protein aggregation by ribosome-associated chaperones. The goal of this research is to investigate how physiological changes regulate protein-based inheritance in yeast. Protein-based heritable elements, in particular fungal prions, are novel kind of genetic elements; they produce heritable changes in their host cells without any change in the DNA of their genes. This occurs by switching between protein isoforms, one of which (prion isoform) is able to reproduce itself by inducing other molecules of the same protein to switch into the same isoform. This project examines how these transitions are aided by another class of proteins, molecular chaperones, whose normal function is to promote correct protein folding and prevent misfolding. Understanding the physiological control of protein-based inheritance may have an impact on the industrial use of yeast and other fungi. The research team includes graduate and undergraduate students and will strengthen the research infrastructure of Georgia Tech.
In August, Biology assistant professor Will Ratcliff and his collaborators received a three year, $562,000 NASA grant to investigate the origin and evolutionary consequences of multicellular life cycles. All multicellular organisms exhibit a characteristic life cycle that alternates between stages of reproduction, growth and development. This life cycle is critical for the evolution of multicellular complexity, playing a central role in transporting fitness from cells to multicellular individuals. Despite their importance, the evolutionary origins of multicellular life cycles are poorly understood. A key factor limiting progress has been the fact that evolutionary transitions to multicellularity on Earth have been both ancient and rare. Using a combination of synthetic biology and experimental evolution, we have created novel multicellular organisms in fungal and algal model systems. This gives us a unique opportunity to investigate the origin of multicellular life cycles, and assess their role in the evolution of complex life.
Carrie Poppy, Tech Times
Read the Article in Tech Times
Biologists want to manipulate your mouth to do something extraordinary: grow extra teeth. And they're getting their advice from fish.
In the developed world, we often take for granted just how important having healthy teeth is. But in cultures without widespread dental care and fluoridation, the situation can be dire. Worldwide, 30 percent of people will lose all of their teeth by the time they're 60. So while it might sound freaky to convince your jaw to make extra incisors, it could actually vastly improve many people's lives. And fish can already do it.
Much like stem cells in humans, certain fish have special cells in their mouth that are extremely flexible; they can form teeth or taste buds, depending on the animal's needs. As a result, cells that are laying dormant can be triggered and differentiated as soon as the fish loses a tooth. That's a lot more clever and adaptive of a system than what humans have: two sets of teeth and no wiggle room if you lose them.
"There appear to be developmental switches that will shift the fate of the common epithelial cells to either dental or sensory structures," said Todd Streelman, a professor in the Georgia Tech School of Biology, and coauthor of the study, in a press release. In other words, there appears to be an on/off switch inside every fish's mouth cells. Flip it, and the cell becomes a tooth, leave it, and it becomes a taste bud.
The Georgia Tech researchers, along with scientists from King's College London, are studying the embryos of fish called cichlids, who live in Lake Malawi, home to one of the most diverse fish populations in the world. There are over 1,000 cichlid species in the lake, alone. Because there are so many species of these fish in a relatively small area, they have varying adaptations that inform the development of their teeth. Some eat plankton, and only need a few teeth over their lifetimes. Others eat algae, which they have to scrape off of rocks like so much corn on the cob, ruining their teeth as they go. They have to develop new teeth all the time.
By comparing these species and checking out the differences in their DNA, the scientists were able to single out the mutations that make it possible to grow extra chompers. Now, the next step is to figure out how the same can be triggered in mammals. But they (probably) won't be actually engineering your grandkids to grow extra teeth.
"The more we understand the basic biology of natural processes, the more we can utilize this for developing the next generation of clinical therapeutics: in this case how to generate biological replacement teeth," explained Professor Paul Sharpe, a coauthor from King's College. That could come in the form of cell cultures, laboratory animals or, less likely, turning future generations into fishy freaks.
The study was published in the Proceedings of the National Academy of Sciences of the United States.
Dr. Chrissy Spencer was appointed an OER Research Fellow for 2015-2016. The William and Flora Hewlett Foundation sponsors OER Research Fellowships to do research on the impact of open educational resources on the cost of education, student success outcomes, patterns of usage of OER, and perceptions of OER. The OER Research Fellowships are competitive, and OER grants are administered and supported by the Open Education Group.
Emily Singer, Quanta Magazine
View the Artcile in Quanta Magazine
Until one or two billion years ago, life on Earth was limited to a soup of single-celled creatures. Then one fateful day, a lonely cell surrendered solitude for communal living. It developed a chance mutation that made its progeny stick together, eventually giving rise to the first multicellular life.
With that simple innovation, a world of possibilities burst open. These new organisms were too big to be eaten, and their mammoth size allowed them to pull in more food from the environment. Most important, individual cells within the bunch could begin to specialize, taking on new functions, such as hunting, eating and defense. The transition to multicellularity was so successful that it happened over and over again in Earth’s evolutionary history — at least 25 times, and very likely more.
Multicellularity has clear advantages — just look at the menagerie of form and function among animals, plants and fungi. But scientists have long been puzzled as to how this transformation took place. A true multicellular organism acts as a unit, meaning that each cell must surrender its will to survive as an individual and act to ensure the survival of the larger group. “The problem with all the major evolutionary transitions is how Darwinian entities relinquish their individual fitness and become part of a higher-level unit,” said Richard Michod, an evolutionary biologist at the University of Arizona in Tucson.
Scientists are gaining insight into the process by re-creating the evolution of multicellularity in the lab. Using an approach known as experimental evolution, they prod single-celled microbes, such as yeast, algae or bacteria, to develop a multicell form.
“It’s easy to think of [these major transitions] as a giant leap in evolution, and in some sense that’s true,” said Ben Kerr, a biologist at the University of Washington in Seattle and one of the researchers studying major transitions in evolution. But each transition actually involved a series of small advances — the organisms had to evolve effective ways to stick together, to cooperate, to divide and to develop specialized jobs within the greater whole. “We’re trying to do the opposite of a giant leap. We’re trying to break one giant leap for evolution into an understandable series of small steps.”
William Ratcliff, a biologist at the Georgia Institute of Technology in Atlanta, and his collaborators have discovered a surprisingly simple route to multicellularity: a single mutation in yeast that adheres the mother cell to its daughter to create a snowflake-like shape. These snowflakes grow and divide in a way that provides a clever solution to one of the major pitfalls of multicellularity: the cheater problem, in which lazy cells take advantage of cooperative ones. And while the work hasn’t produced a true multicellular organism, the snowflake yeast has shown just how easy it can be for life to take the first step toward a major biological transformation.
Ratcliff began his quest for multicellularity while still a graduate student at the University of Minnesota. Over a series of coffee-fueled conversations, Ratcliff and his collaborator Michael Travisano began brainstorming the “coolest experiment we could do,” according to Ratcliff. Tackling the biggest unsolved question in biology — how life first began — was too far out of their wheelhouse, the pair decided. So they settled on the runner-up: How did multicellular creatures evolve? To untangle that transition, the researchers would try to re-create it, converting single-celled yeast into multicellular organisms.
Ratcliff and Travisano developed an easy way to force yeast to become multicellular. They grew the microbes in tubes and spun them in a centrifuge once a day. The largest cells or those that clustered together sank the fastest. Each day, they selected the fastest sinkers, challenging those cells to another round of the experiment. Over the course of 24 hours — roughly seven generations of yeast — the cells accumulated tens of thousands of mutations.
Then, a couple of weeks into the experiment, the composition of a few of the tubes suddenly changed. The cells began forming large clusters, and the silky solution of single cells transformed into grainy blobs. Within 100 yeast generations — about two weeks — the population had shifted almost entirely to snowflake yeast.
“I was gobsmacked,” Ratcliff said. “It was unusual, fast and dramatic.” Peering at the solution under the microscope revealed that single cells were now in the minority. “We mostly saw these beautiful spherical branched things.”
While typical yeast divides and disperses after each generation, snowflake cells divide and stick. Daughter cells cling to their mother like baby kangaroos. Mother and daughters then divide again and again, each producing another attached offspring.
The evolution of snowflake yeast created more than a mere clump of cells. Wild yeast strains sometimes produce a sticky protein on their surface, which makes the cells adhere to each other. Brewers like this sticky form, known as floc yeast, because it’s easier to remove it from newly brewed beer.
But snowflake yeast is quite different from flocs. Floc yeast cells divide and separate, then condense into a genetically diverse pile. Snowflake yeast grows in highly related clumps. It’s this difference that Ratcliff and others say distinguishes a simple blob of cells from a cohesive unit capable of evolving true multicellularity.
Whether snowflake yeast qualifies as truly multicellular or not is a difficult question to answer. There’s no clear dividing line between single-celled and multicellular organisms. Ratcliff likens the transition to what he calls the rich man, poor man problem. If you gathered everyone in the United States and lined them up according to wealth, the richest people would land at one end and the poorest at the other. If you just looked at these extreme ends of the spectrum, it would be easy to define the characteristics of the rich and the poor. But if you drove down the line of people, it would be impossible to define a strict point where the rich group ended and the poor group began. By this analogy, snowflake yeast is in the multicellular middle class.
The Nature of Individuality
Around Christmas six years ago, Ratcliff slid a photo of his snowflake yeast under the door of a historian colleague who studies the nature of individuality and asked him to identify the individuals: Were they the single cells that made up the snowflakes, or the snowflakes themselves? The historian drew Santa hats on the snowflakes, a tongue-in-cheek method of choosing the multicellular entities.
Ratcliff was trying to get at the question of how to define an individual, one of those superficially simple questions that are actually quite complex. And while biologists don’t agree on the exact qualifications that designate an individual, they do have a broad set of guidelines. Snowflake yeast satisfies a number of important requirements.
First, individual cells within a snowflake appear to sacrifice themselves to benefit the whole. When snowflake yeast reaches a certain size, cells within the clump commit suicide, releasing smaller daughter clumps from the parent cluster. “It’s deeply poetic: The death of individual cells seems to be a direct contributor to the birth of new multicellular organisms,” Kerr said. The process illustrates the beginnings of a division of labor within the organism. Individual cells have distinct roles to play, even if their role is simply to die. “It’s not in the interest of the individual cell — it’s shifted interest to a higher level.”
Snowflake yeast also mirrors the genetic bottleneck that we all go through. Every one of us began as a single cell, a fertilized egg that produced the complex layers of tissue that make up our bodies. Each daughter branch in snowflake yeast is composed of cells that originated from the same parent cell. In both cases, the resulting block of cells is genetically identical, or nearly so.
That homogeneity is essential for blocking the spread of cheater cells, the single-celled equivalents of lazy roommates who eat everyone’s food but never go shopping or pay the bills. Cheater microbes steal resources from their neighbors and devote all their energy to reproduction, rapidly outnumbering the more industrious cells. (Cancer is an example of cheaters within our own bodies — genetically distinct cells that act in their own best interest, endangering the larger entity.)
In snowflake yeast, the single-cell bottleneck means that cheater cells are stuck with a community of cheaters. The group won’t be able to survive on its own. “The simplest and most general explanation for why multicellular organisms pass through a single-cell stage is to ensure that all the cells composing the organism are as close to perfectly related to each other as they could be,” said Rick Grosberg, an evolutionary biologist at the University of California, Davis. “Everyone shares the same genetic interests.” The bottleneck forces an alliance.
Perhaps the most important argument in favor of snowflake yeast’s status as a multicellular creature is that natural selection is acting on the snowflake as a whole. In a new set of experiments, Ratcliff’s team is pitting snowflake yeast against floc yeast in a head-to-head battle. Preliminary results show that over and over again, snowflakes drive flocs to extinction. “They are evolving in the same way that multicellular organisms are,” Ratcliff said. “Selection acts on groups and the groups respond to selection.”
Yet snowflake yeast fails one key test of multicellularity: indivisibility. “We can’t be chopped into smaller parts and maintain the properties of the whole,” Michod said. Snowflake yeast can. Because of this, “I think snowflake yeast are not really true multicellular organisms,” Michod said. “But they are certainly on their way.”
The snowflake yeast strains have now been evolving for more than a year, and they continue to change, getting bigger and rounder with each generation and sinking faster than their ancestors. “We can see these Darwinian processes playing out in the lab over thousands of generations,” Ratcliff said.
The ongoing transition is giving researchers a powerful tool for studying the genetic foundations of multicellularity. Ratcliff has already identified one of the genetic mutations that make it possible for snowflake yeast cells to stick together in their particular way. He hopes to identify additional mutations involved in the switch to multicellularity, which will illuminate the mechanisms underlying the process. Even though snowflake yeast might not directly reveal how multicellularity first evolved on Earth, it should highlight the general evolutionary processes needed to get there. The fact that basic multicellularity is so easy to create is “a profound insight if not a complete insight,” Grosberg said.
What’s more, lab-evolved multicellularity isn’t limited to yeast. Scientists can drive other single-celled organisms to multicellularity as well. Ratcliff and collaborators Matthew Herron and Frank Rosenzweig, both biologists at the University of Montana in Missoula, showed that they can transform the single-celled alga Chlamydomonas reinhardtii into a multicellular entity. This is particularly important because one of the criticisms of Ratcliff’s yeast work is that some natural yeasts have multicellular forms, meaning that his experiments might simply be restoring a latent talent.
The researchers ran similar experiments to those in yeast, selecting for cells that sink the fastest. But they also employed a selective pressure that algae are more likely to experience in nature: predators, such as paramecia, that can’t eat larger multicellular blobs. The predator-driven strains developed a different sort of multicellularity from the gravity-induced versions. These multicellular Chlamydomonas have spherical blobs of cells contained within the same cell wall.
It’s not so surprising that algae came up with different routes to multicellularity. The transformation evolved independently in plants, animals and fungi dozens of times, maybe more. So there are likely different solutions to the problem of making the transition. “What are the suite of possible genetic keys that unlock the door to multicellularity?” Rosenzweig said. “That’s one thing to be gained by comparing different systems.”
Researchers also want to know how these clusters become more complex, partitioning jobs like a well-run factory. “How does a multicellular organism make that next great leap to differentiated cell types that work cooperatively in the organism?” Rosenzweig said.
Rosenzweig cites an ongoing experiment in his lab with Chlamydomonas. Single-celled algae have flagella, taillike appendages that propel the cell toward light. The multicellular versions of Chlamydomonas also have flagella, but theirs are trapped and useless inside the larger cell wall. “It’s like being in a lifeboat and having your oars stuck in the air, not the water,” Rosenzweig said. To use their flagella, Chlamydomonas will have to evolve ways to get them in the right place and to coordinate their movement.
Ratcliff hopes his snowflake yeast will eventually develop this kind of complexity. Perhaps the mechanism that drives cell suicide will evolve a more sophisticated function. Perhaps, given enough time, the new multicellular forms will evolve even more surprising capabilities, just as the transition to multicellularity billions of years ago ushered in a world of large and complex life. “One of the reasons the research is so interesting is that it describes the beginning of a bona fide major transition in real time,” Kerr said.
By Shelley Littin, iPlant Collaborative
Original Story: http://www.iplantcollaborative.org/blog/news/iplant-hosts-platform-field...
Researchers led by a team at the Georgia Institute of Technology (Georgia Tech) have developed an online platform that enables plant scientists to obtain quantitative phenotype information on the root systems of plants imaged in the field.
The platform, called Digital Imaging of Root Traits (DIRT), is now hosted by the iPlant Collaborative’s computational infrastructure, as described in a recent publication in the journal Plant Methods. Researchers anywhere in the world with an Internet connection can access the program by logging into an iPlant account.
The idea is to expedite and simplify the process of collecting measurements of plant roots in the field, said Alexander Bucksch, a research scientist in Joshua Weitz's group at Georgia Tech, and corresponding author on the paper. “Visual phenotypes of a plant can be computed reproducibly with imaging, including features impractical to measure by hand,” Bucksch explained.
The research team spent three years collecting plant root samples at field stations in the United States and South Africa and manually measuring dozens of traits including root density, angles, surface area, number of roots, and many more. They then configured calculations based upon these standardized measurements, to produce a program capable of giving highly accurate measurements for root traits based upon a photograph of roots.
To use the platform, a scientist need only lay out the roots next to a marker for scale and take a photograph, and the program will provide many dozens of phenotype measurements. “DIRT provides a pipeline to move from a field-based image to quantitative data as part of studies by academics and breeders alike,” said Joshua Weitz, associate professor of biology and director of the Quantitative Biosciences Graduate Program at Georgia Tech.
In response to broad interest in using DIRT in the field, Bucksch and his colleagues approached iPlant to host the platform and make it freely available to researchers anywhere. Through iPlant, a user’s data are secure, so that only the account owner and their collaborators may see the results. This makes DIRT a secure, open-access, time saving tool for botanists everywhere.
“Field-based measurements are vital for quantifying traits,” said Nirav Merchant, co-principal investigator of the iPlant Collaborative at the University of Arizona’s BIO5 Institute, and director of Biocomputing at Arizona Research Laboratories. “Automating these methods is essential to support the high throughput nature of analysis. For scientists in the field, DIRT elegantly facilitates the analysis and management of image-based phenotype data by connecting them with scalable cyberinfrastructure and their global community of collaborators.”
“Manually,” Bucksch said, “you cannot measure many dozens of traits in just five minutes, as you can with DIRT.”
The program currently works for nearly all plant root systems. “There are certain traits that only work on monocots or dicots, and we are currently exploring more about this,” Bucksch said, explaining that slight differences in the algorithms account for variation in the plant species.
Already the platform has a substantial user base, with several scientists regularly using it for their root measurements. “Undergraduate students are using DIRT, a Google group is providing user-to-user support, and at least one citizen scientist is currently using it,” said Bucksch.
"DIRT seems especially useful in my work because a plant is a lot like an iceberg: Most of it is totally hidden beneath the surface," said Tim Zebo, a recently retired electronics engineer turned hydroponics and aeroponics systems researcher. Dr. Zebo is analyzing the roots of plants grown in liquid nutrients because, in this era of rapid climate change and major droughts, those plants require less than 10 percent of the water needed for soil-grown plants. He plans to use DIRT to better understand root system architectures to increase production and reduce time to harvest.
For plant scientists and breeders, Bucksch said, root traits are key. “The root is important to nutrient uptake,” he said, continuing “and understanding how environmental and growth factors influence root traits is vital to developing crops capable of surviving climate change.
Increased food availability and resilience is necessary to accommodate accommodate rapidly increasing global populations. Plant scientists must work together to understand how plant traits – including root structure and function – affect crop survivability and adaptability. Bucksch and co-authors have developed DIRT with this objective in mind and to enhance the science of root systems.
Their work was supported, in part, by grants from Georgia Tech, the National Science Foundation, the Howard G. Buffett Foundation and the Burroughs Wellcome Fund. Bucksch also thanks iPlant co-principal investigator Nirav Merchant and iPlant senior projects coordinator Martha Narro for their assistance integrating DIRT on iPlant infrastructure. Abhiram Das, a graduate student studying under Bucksch and Joshua Weitz at the Georgia Institute of Technology, led the effort to develop DIRT prior to receiving his doctorate in Bioinformatics earlier this year.
Associate Professor Joshua Weitz has published the first comprehensive book on quantitative viral biology. Quantitative Viral Ecology: Dynamics of Viruses and Their Microbial Hosts establishes a theoretical foundation for modeling and predicting the ecological and evolutionary dynamics that result from the interaction between viruses and their microbial hosts. These go well beyond the viruses we most often think of—influenza, HIV, and Ebola—and include the diverse and abundant viruses that infect single-celled microbes found in oceans, lakes, plants, soil, and animal-associated microbiomes.
Weitz's book addresses three major questions: What are viruses of microbes and what do they do to their hosts? How do interactions of a single virus-host pair affect the number and traits of hosts and virus populations? How do virus-host dynamics emerge in natural environments when interactions take place between many viruses and many hosts? Emphasizing how theory and models can provide answers, Weitz offers a cohesive framework for tackling new challenges in the study of viruses and microbes and how they are connected to ecological processes—from the laboratory to the Earth system.