Stem Cell Plasticity in Tissue Repair and Regeneration Collection

 

We are excited to publish a collection entitled Stem Cell Plasticity in Tissue Repair and Regeneration, which results from a PLOS ONE’s call for papers announced last year. We encouraged submissions spanning a broad range of biomedical topics, including basic stem cell biology, preclinical research and biomedical engineering. The papers included in the collection provide examples of how the dynamic functions of stem cells can be harnessed to regenerate damaged or lost tissues. Regenerative approaches may offer a unique therapeutic opportunity for diseases where with no established treatments exist.

 

In line with PLOS ONE publication ethos, we welcomed solid and clearly reported studies regardless of the perceived impact and positive nature of the main findings. We think that in the fast-paced field of stem cell research, addressing publication bias is particularly important to advance knowledge and bring new therapies to the clinic.

 

Two studies included in the collection reported the role and regenerative ability of adult mesenchymal stem cells (MSCs). Chung et al. showed the regenerative potential of human MSCs in a rat model of bladder disease. They also identified the bladder submucosa as the most effective route of MSC administration. In a clinical study among patients with acute respiratory distress syndrome, Patry et al. found that extracorporeal membrane oxygenation increased the number of circulating MSCs, although further research is needed to establish the regenerative potential of these cells in the context of pulmonary disease.

 

Bladder tissue regeneration identified via IHC staining pone.0226390

 

Two methodological papers focused on the differentiation of human induced pluripotent stem cells (hiPSCs) into cardiac cells. This rapidly evolving research area aims at overcoming the current challenges in generating mature cells in large quantity and high purity for tissue engineering applications. Rupert et al. described practical methods for the optimization of hiPSC-cardiomyocyte differentiation, highlighting the key role of metabolic selection. Chu et al. demonstrated that cardiac differentiation can be achieved by co-culturing hiPSCs with mature cardiomyocytes, without the addition of exogenous pharmacological agents.

 

Workflows for cardiac differentiation of stem cells pone.0230001

 

This collection was made possible thanks to the fantastic work of our Guest Editors – Michelina Iacovino, Scott D. Olson and Che Connon – who helped develop the scope of the call for papers and evaluated all submitted research for inclusion in the collection. We are also extremely grateful to the members of our editorial board and external peer-reviewers for dedicating their time and expertise to the evaluation of submissions.

 

We will add new papers to the Collection as they are published, so we invite you to check back the collection webpage in the coming weeks. If you are interested in keeping up to date with the latest stem cell research from the broader literature, check out our PLOS Channel too.

 

Guest Editors

Scott D. Olson

Scott Olson is a mesenchymal stem cell (MSC) Biologist working in the Children’s Program in Regenerative Medicine in the Department of Pediatric Surgery at McGovern School of Medicine. Dr. Olson completed his doctorate in the lab of Dr. Darwin Prockop at Tulane University’s Center for Gene Therapy studying novel methods by which MSCs can contribute to tissue repair. At University of California at Davis’s Health Sciences Institute for Regenerative Cures with Dr. Jan Nolta, Dr. Olson worked to apply MSCs as a platform to develop new treatments for Huntington’s Disease. Dr. Olson joined UTHealth in September 2011.

 

Dr. Olson is involved in developing and transitioning studies with direct translational applications. At UT Health, his primary focus is bringing his expertise in the field of adult stem cells, specifically MSCs, to explore their potential in the treatment of Traumatic Brain Injury (TBI) and in trauma-associated neuroinflammation in general. MSCs have been used in a number of completed, ongoing, and proposed clinical trials with reported therapeutic benefits. Dr. Olson strives to better describe the role of MSCs in injuries of the central nervous system, highlighting their innate therapeutic abilities in an effort to create an improved treatment for TBI.

 

Michelina Iacovino

Michelina Iacovino is an Assistant Professor at the David Geffen School of Medicine at The University of California, Los Angeles (UCLA), and a Principal Investigator at Los Angeles Biomedical Research Institute (LABioMed) at Harbor-UCLA in the Pediatrics Department.

She obtained her Doctorate in Italy in Biochemistry and Applied Chemistry working on mitochondrial DNA inheritance in yeast in collaboration with Dr. Ronal Butow at the University of Texas Southwestern Medical Center. She then trained in the field of hematopoietic stem cells with Dr. Michael Kyba during her postdoctoral fellowship, studying the role of Hox genes during blood development. She joined LABioMed in 2012, extending her expertise of stem cell biology to develop treatments for rare lysosomal disorders that affect brain function. She is currently developing a stem cell therapy for Sanfilippo syndrome, an incurable and rare lysosomal disorder, using neural progenitor cells.

 

Che Connon

Che Connon obtained his PhD in Biophysics from the Open University Oxford Research Unit in 2000, during which time (under the supervision of Professor Keith Meek) he investigated corneal wound healing and transparency. He subsequently obtained a JSPS post-doctoral fellowship to work with Professor Shigeru Kinoshita in Kyoto, Japan for two years studying corneal stem cell transplantation. Upon his return to the UK he was awarded a Royal Society Fellowship to investigate the use of biomaterials in stem cell therapies. He obtained his first permanent position in 2007 at University of Reading, School of Pharmacy and since 2014 he has held the position of Professor of Tissue Engineering at Newcastle University.

Professor Connon’s research team seeks to engineer functional replacement and temporary ‘bridge’ tissues using a modular approach while also developing model systems to study physiological and pathophysiological corneal tissue formation. He is currently working with smart (cell responsive) biomaterials, characterizing the mechanical and geometric environment of the corneal stem cell niche and 3D printing the corneal stroma.

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Introducing the Life in Extreme Environments Collection

Written by Daniel Colman (Guest Editor, Montana State University), Ruth Blake (Guest Editor, Yale University) and Hanna Landenmark (Associate Editor, PLOS ONE).

We are delighted to introduce a Collection entitled Life in Extreme Environments, consisting of papers published in PLOS Biology and PLOS ONE. This interdisciplinary Collection helps us better understand the diversity of life on Earth in addition to the biological processes, geochemistry, and nutrient cycling taking place in many of the Earth’s most inhospitable environments, while also enabling us to make inferences about the potential for life beyond Earth. Microorganisms and other life in extreme environments are fundamental agents of geochemical and nutrient cycling in many of the most poorly understood environments on Earth. While we tend to think of these environments as lying at the boundaries of what life is capable of dealing with, many organisms are uniquely adapted to thrive in habitats at the extremes of temperatures, pressures, water availability, salinity, and other environmental characteristics. Indeed, these environments are certainly not “extreme” to these organisms, but represent their unique niches within ecosystems on Earth. The papers included in this Collection bring together research from different disciplines including the biosciences, geosciences, planetary sciences, and oceanography in order to shed light on this crucial topic.

We are immensely grateful to our Guest Editor team- Paola Di Donato (Università degli Studi di Napoli “Parthenope”), Jiasong Fang (Hawaii Pacific University), David Pearce (Northumbria University), Anna Metaxas (Dalhousie University), Henrik Sass (Cardiff University), Ruth Blake (Yale University), Daniel Colman (Montana State University), Karen Olsson-Francis (The Open University), Frank Reith (The University of Adelaide), Felipe Gómez (Centro de Astrobiología, Instituto Nacional de Técnica Aeronáutica)- for curating this Collection.

The importance of studying life in extreme environments

It is important to study life in extreme environments in order to establish life’s limits – both physical and geographic (e.g., the depth of life beneath the seafloor), as well as the capacity of life to withstand and adapt to change. Besides significantly expanding our understanding of the limits of familiar and extreme life on Earth, studies in extreme environments have also revised our understanding of the nature of the earliest life on our planet, as well as providing the possibility of discovering new industrially useful organisms or biological products. Moreover, if there is life on other planetary bodies in our solar system or elsewhere, they will almost certainly be living in what we consider “extreme environments” on Earth. Thus, understanding how life copes with what we consider extreme conditions can provide insight into how life may be able to persist on other planetary bodies, perhaps in the subsurface oceans of Saturn’s moon, Enceladus, or Jupiter’s moon, Europa.

Investigating extreme life

One of the most exciting aspects of researching extreme life is the exploration of the unknown and discovery of new things in unexpected places that expands our very way of thinking. Microbial life, in particular, has evolved to find a way to exist and even thrive pretty much everywhere we have looked so far. Moreover, contemporary research of extremophiles is happening at an exciting time when the lines between scientific fields have been increasingly blurred. The more we understand about how environments not only influence life in extreme environments, but how life also influences those environments, the more apparent it becomes that extreme ecosystems are dynamic systems with feedback between biological activities and ecosystem properties. These interdisciplinary perspectives certainly invigorate the study of extreme life.

Extremophile research is often interdisciplinary by nature, perhaps due to the close association with biological organisms and their ecosystems, and thus the need to consider environmental, geologic, ecological, physiological, and even evolutionary considerations when investigating how organisms are able to push the limits of life. The challenges can be considerable due to the need to integrate across many disciplines, which requires expertise in a number of areas (and requiring scientists across disciplines to productively engage one another). But the reward for conducting this type of research is that it can transform how we view the relationships between living organisms and their environments. These insights can be profound in terms of our understanding of organismal biology and broader evolutionary processes of adaptation.

Yet, by their very nature, extreme environments pose significant challenges for studying biological life within them. This can be due to their remote locations (e.g., deep sea environments, high altitude environments), or to specific dangers associated with studying them (e.g., geothermal fields or other volcanic environments). Indeed, the reason that these environments are considered “extreme” is because they are not amenable to humans spending much time within them. It takes serious dedication and preparation to execute scientific research under such conditions.

The future of extremophile research

The last 30-40 years have reshaped our understanding of life in extreme environments, but much remains to be discovered. As one example, we’re still only beginning to understand what types of microbial life can exist in extreme environments, let alone what the physiological adaptations of these organisms might be. One of the greatest questions in the study of life in extreme environments i whether life is present in other “extreme environments” of the Universe beyond our planet. While we cannot know whether answers to this question will be forthcoming in the near future, great strides are being made in pointing us in what may be the most likely directions.

The Life in Extreme Environments Collection

This Collection showcases a wide variety of research on how life, from microorganisms like bacteria, archaea, diatoms, and algae, through to macroorganisms like humans, survive and flourish in diverse extreme environments, ranging from hydrothermal vents and the deep ocean to permafrosts and hypersaline lakes, and from the high Andes to deep space. Many papers illustrate highly interdisciplinary approaches and collaborations, and provide important insights into the limits of life on Earth in truly extreme environments. As indicated above, extremophiles provide insight into far-ranging topics like the limits of life on Earth, biogeochemical cycling in extreme but globally important environments, insights into early life on Earth, and how organisms cope with conditions that push the boundaries of organismal physiology.

A critical component of extremophile research is understanding how extremophiles are distributed across environments in both contemporary settings as well as over geologic time. Serpentinizing environments are considered to be analogs for the environments where life originated on Earth (and that may also support life on other planetary bodies). The investigation of fully serpentinized rocks by Khilyas et al. document the endolithic (i.e., within-rock dwelling) microbial diversity within these unique environments, their associations with their mineral environments, and contrast their findings with those of active serpentinizing aqueous environments. Such studies examining the connection between extreme environments and their native microbiomes can be critical for understanding how organisms have and continue to interact with their environments over time. Another study in the Collection by Kiel and Peckmann provides new insights into the association of macrofauna with hydrothermal vents over the past ~550 million years. Their survey of dominant brachiopod and bivalve fossils over this period challenge the pre-existing hypotheses that these two groups competed for the same resources, with the latter group ultimately gaining prominence in the last ~100 million years. However, the authors show that the two groups likely inhabited different vent environments altogether, with brachiopods inhabiting hydrocarbon seeps and bivalves preferring sulfide-producing vents in association with their symbiotic sulfide oxidizing bacteria. To better understand the contemporary distributions of important marine microorganisms, Ferreira da Silva et al. documented how diatom communities are associated with macroalgae in the waters near the South Shetland Islands of Antarctica, revealing a potential role of the unique Antarctic climate in determining the biogeography of diatoms and their associated macroalgae. Indeed, the relationships among organisms may be critical for the habitation of extreme environments. In another investigation of cross-taxa associations in extreme environments, Gallet et al. evaluated the diversity of microbiota associated with enigmatic bioluminescent lantern fish species, and found that the latter might interact with its microbiome to inhabit the extreme environment of deep southern oceans. The data provide a better understanding of these important associations in key species involved in the ecosystem function of extreme deep sea environments.

Although extreme environments are often considered marginal habitats of mostly local influence, the functions of some extreme environments, and the organisms inhabiting them, can have particularly important implications for global biogeochemical cycling. For example, Nayak et al. document new insights into the functioning of one of the most important microbial enzymes involved in global carbon cycling, the methyl-coenzyme M reductase protein of methanogens, which catalyzes the key step of methanogenesis allowing the biological production of methane, which contributes to a significant portion of global methane production. In the authors’ investigation, they show how the protein is post-translationally modified by a previously unknown mechanism, and that this ‘tuning’ of methyl-coenzyme M reductase has profound impacts on the adaptation of methanogens to various environmental conditions. Anoxic peatlands are one such environment where methanogens play critical roles in biogeochemical cycling. These anoxic peatland environments are extreme environments that are important for global biogeochemical cycling, despite only occupying a small fraction of the total land space. Kluber et al. used an experimental warming approach to investigate how deep, anoxic peatland reserves would respond to fluctuating environmental conditions. The authors document that temperature is a key parameter that could drastically affect the decomposition of peatland nutrient stocks and their contribution to global biogeochemical cycling.

Key to the interaction between organisms and extreme environments are the adaptations that extreme environments impose upon organisms. The Collection features a number of investigations documenting the unique adaptations of microorganisms and macroorganisms to habitats ranging from hydrothermal vents to space at both the genomic and physiological levels. One of the most enigmatic discoveries of extreme environments over the past half century was the identification of entire ecosystems that dwell on or around hydrothermal vents at the ocean floor that are sustained by inorganic chemical synthesis from hydrothermal vent fluid chemicals. The paper within this Collection by Zhu et al. provides new evidence for the genetic mechanisms that allow the habitation of vent ecosystems by two distinct shrimp species that characteristically inhabit different thermal regions of vents. Using transcriptomic approaches, the authors identified new molecular mechanisms underlying how macrofauna can adapt to different hydrothermal niches within these extreme systems. Likewise, Díaz-Riaño et al. used transcriptomics to identify the mechanisms of ultraviolet radiation resistance (UVR) within high UVR bacterial strains that were isolated from high altitudes within the Colombian Andes. These new insights provide much needed resolution into the RNA-based regulatory mechanisms underlying UVR in organisms, which represents a fundamental knowledge-gap in our understanding of organismal adaptations to extreme altitude environments.

While life that persists continuously under extreme environments provide valuable information to understand the physiological limits of life, it is also critical to understand how life adapted to more ‘normal’ environments can withstand excursions to extreme environments over prolonged periods of time. One such example are oxygen minimum zones that occur in deep oceans where oxygen levels have been depleted to levels thought to not be able to support higher life, in what is termed ‘hypoxic conditions’. Nevertheless, some higher organisms are capable of living in such environments, although their adaptations to this lifestyle are not currently clear. One such species is the bluntnose sixgill shark that can tolerate very low levels of oxygen. Using an array of biologging techniques that allowed them to monitor the physiological and behavioral activities of these sharks, Coffey et al. provide evidence for their migratory behavior and long periods of exposure to hypoxic conditions in the deep sea. In addition to elucidating how sixgill sharks cope with extreme deep sea conditions, the new ecophysiological logging techniques provide a new platform for future studies of organisms adapted to the extremes of deep oceans. Among the possible excursions of life to extreme environments, none are potentially more problematic than the travel of humans to space. A common physiological effect of space transit is the bone mineral density (BMD) loss that is experienced by astronauts. In a paper within the Collection, Axpe et al., performed a modeling analysis based on BMD loss by previous astronauts involved in long-term missions in order to evaluate the potential for these harmful effects on trips that might become targets for longer manned missions to Mars or elsewhere. The study thus provides critical new data to inform these important missions.

As exemplified by the papers within this Collection, unique adaptations allow life to persist in extreme environments. These adaptations can also be useful in biotechnological applications, as several other papers in the Collection demonstrate. Halophiles that inhabit extremely saline environments have long been a source for bioprospecting due to their unique adaptations that allow them to maintain osmotic balance within environments that most types of life could not survive in. Notably, halophiles often concentrate unique biomolecules in order to overcome the abiotic stress of hypersaline environments. In their manuscript, Abdollahnia et al.  explore the previously little-investigated ability of halophiles to concentrate nanoparticles, finding evidence for the unique ability to concentrate metal nanoparticles within archaeal and bacterial species. Importantly, these organisms could represent a potential environmentally-friendly means of synthesizing unique metal nanoparticles. Thus, the identification of new bio-resources is an area of ongoing and intense interest in the investigation of extreme life.

As is evident by the diverse range of topics, organisms, and environments within the papers of this Collection, the investigation of extreme life incorporates numerous fields of study and a wealth of methods to understand the limits to life on Earth. We’ll be adding new papers to the Collection as they are published, so please do keep checking back.

About the Guest Editors

Ruth Blake

Ruth Blake is a Professor in the departments of Geology & Geophysics and Environmental Engineering, and in the School of Forestry & Environmental Studies at Yale University. Dr. Blake’s areas of expertise include marine biogeochemistry, stable isotope geochemistry and geomicrobiology. Her recent work focuses on developing new stable isotope tools, geochemical proxies and biomarkers to study marine/microbial phosphorus cycling and evolution of the phosphorus cycle from pre-biotic to recent.

Dr. Blake is engaged in a range of studies on co- evolution of earth and life and the impacts of both on biogeochemical processes occurring in the oceans, deep-sea sediments, seafloor hydrothermal systems and the sub-seafloor deep biosphere. Dr. Blake has participated in several ocean exploration/ research expeditions including cruises to: FeMO observatory at Loihi undersea volcano, 9°N EPR, Orca Basin in the Gulf of Mexico and North Pond in the mid-Atlantic. She has also served as shipboard scientist on Ocean Drilling Program and R/V Atlantis /DSV ALVIN platforms. Ruth Blake graduated from the University of Michigan in 1998 with a PhD in geochemistry.

Daniel Colman

Dan is currently an assistant research professor at Montana State University and is an environmental microbiologist with primary research interests in broadly understanding how microbial populations interact with one another and with their environments. To investigate these broad topics, he uses a suite of interdisciplinary techniques at the intersection of environmental microbiology, biogeochemistry, geomicrobiology, microbial physiology, geochemistry, hydrology, and microbial evolution.

In particular, his work leverages environmental genomics methods coupled to in situ and laboratory experiments along with geochemical insights from hydrological and geochemical analyses to understand 1) how and why environments structure micobial communities, 2) how microbial communities shape their environments, and 3) how environments and microbial populations have co- evolved through time. In particular, he has largely focused on evaluating these questions in extreme environments, and especially hydrothermal systems, which represent an excellent platform to deconvolute microbial-environment relationships across substantial environmental gradients.

Paola Di Donato

Graduated in Chemistry, Paola received her PhD in 2002 and since 2008 she is a Researcher in Biochemistry at the Department of Science and Technology of University of Naples “Parthenope”; in 2016 she has been appointed as the Dean’s delegate to managing the Institutional Repository of the University “Parthenope”.

Her research interests are the valorisation of waste vegetable biomass and the study of extremophilic bacteria. With regard to the first topic, her research focuses on the recovery of value added chemicals (polysaccharides and polyphenols) and the production of energy (bioethanol) from wastes of vegetables food industry and of dedicated crops (giant reed, cardoon). With regard to the study of extremophilic bacteria, her research activity is aimed at studying the biotechnologically useful biomolecules (enzymes and exopolysaccharides) produced by these bacteria; in the last seven years, particular attention has been paid to the study of extremophiles in relation to Astrobiology, the multidisciplinary approach to the study of origin and evolution of life on Earth and in the Universe.

Felipe Gómez

Dr. Felipe Gómez is a senior staff scientist at the CAB. His research work focuses on the study of extreme environments, limits of life and, by extrapolation, development of habitability potential in adverse environments. He participates in Mars exploration space missions to search for traces of life and study the habitability potential of the red planet. He is currently part of the scientific team (Co-Investigator) of the Rover Environmental Monitoring Station (REMS) instrument aboard the NASA Curiosity-MSL rover that is studying the surface of Mars at this time. Dr. Felipe Gómez is Co-I of MEDA instrument that will be onboard Mars2020 NASA mission to Mars.

He has been part of the scientific team of several campaigns of astrobiological interest in studying different extreme environments. The project M.A.R.T.E. (Mars Analogue Research and Technology Development) began in 2003 and extended until 2006. Its principal investigator was Dr. Carol Stocker of NASA Ames Research Center. This project was funded by NASA within NASA’s ASTEP program for the development of technology for future space missions. This project was developed with the collaboration of several institutions in the United States and CAB. It consisted in the study of the subterranean environment of the zone of origin of the Tinto River (Huelva) where several perforations were made (160 m deeper) until reaching the anoxic zone isolated from the surface. The ultimate goal of the project was the design and development of an automatic platform for drilling without direct human intervention (automatic drilling) on ??the surface of Mars. This project was the beginning of research into the development of automatic drilling instruments for this purpose. It was developed in three phases: first and second year with non-automatic perforations and “in situ” study of the samples that were obtained in real time. In the third year, the automatic platform was implemented.

Jiasong Fang

Jiasong Fang is a professor in the College of Natural and Computational Sciences of Hawaii Pacific University, Distinguished Chair Professor in the College of Marine Sciences of Shanghai Ocean University, and Director of the Shanghai Engineering Research Center of Hadal Science and Technology. Dr. Fang received his Ph.D. in oceanography from Texas A&M University and did his postdoctoral training at the Department of Microbiology of Miami University.

His scientific interests are primarily in the areas of high-pressure microbiology and biogeochemistry, focusing on piezophilic microorganisms and their role in mediating biogeochemical cycles in the deep ocean and the deep biosphere. He has co-authored 100 scientific publications.

 

Anna Metaxas

Dr. Anna Metaxas is a Professor in Oceanography at Dalhousie University. She received a B.Sc. in Biology from McGill University in 1986, a MSc in Oceanography from the University of British Columbia in 1989 and a PhD from Dalhousie University in 1994. She was a Postdoctoral Fellow at Harbor Branch Oceanographic Institution from 1995 to 1997, and a Postdoctoral Scholar at Woods Hole Oceanographic Institution from 1997 to 1999.

Her research focuses on the factors that regulate populations of benthic marine invertebrates, particularly early in their life history. She uses a combination of approaches, such as field sampling, laboratory experiments and mathematical modelling, to study organisms of ecological and economic importance, including invasive species. She has worked in a variety of habitats from shallow rocky subtidal regions to the deep-sea, including hydrothermal vents and deep- water corals, in temperate and tropical regions of the world. Her research has implications for marine conservation, such as the establishment and success of conservation areas for benthic populations.

Karen Olsson-Francis

Dr. Karen Olsson-Francis is a Senior Lecturer at the Open University, in the United Kingdom. Her research focuses on understanding the role that microorganisms play in biogeochemical cycling in extreme environments. She is interested in this from a diversity and functional prospective. In particular, she has focused on studying terrestrial analogue sites and utilizing this information to understand how, and where, potential evidence of life can be found elsewhere in the Solar System.

 

 

 

 

David Pearce

The underlying theme of David Pearce’s research is to use microbiology (and in particular novel molecular techniques applied to microbial ecology, microbial biodiversity and activity, environmental genomics, biogeochemical cycling and model extremophiles) to understand Polar ecosystem function and the potential for shifts in biogeochemical activity that may result from environmental change. He has taken the lead in the development of new frontiers of research in metagenomics, chemosynthetic communities, sediment sequestration of carbon and subglacial lake environments and have initiated new interdisciplinary approaches on the aerial environment (with chemists), ice nucleation activity (with physicists) and in the biogeochemistry of ice (with glaciologists).

Frank Reith

Frank Reith is an Associate Professor in geomicrobiology at the School of Biological Sciences at University of Adelaide and CSIRO Land and Water, where he heads the Microbes and Heavy Metal Research Group. He holds a PhD in Earth Sciences from the Australian National University. He is interested in microbial processes that affect metal cycling and the formation of new minerals. In turn, he also studies how microbes are affected by elevated concentrations of heavy metals in extreme environments. His particular interests lie in the biomediated cycling of noble/heavy metals, e.g., gold, silver, platinum, uranium, osmium and iridium.

An important aim of the fundamental processes understanding created by his research is to use it to develop tools for industry, e.g., biosensors and bioindicators for mineral exploration, as well as biotechnological methods for mineral processing and resource recovery from electronic waste. Thereby, his approach is highly multidisciplinary and covers field expeditions to remote corners of the Earth, synchrotron research, meta-genomic and proteomic approaches as well as statistical-, geochemical- and reactive transport modelling.

We were very saddened to hear of Frank’s passing before this Collection published. We are immensely grateful for his contributions to PLOS and to his field of research, as well as for his enthusiasm and kindness. Our thoughts go out to his family and friends.

Henrik Sass

Dr. Henrik Sass is senior lecturer in Geomicrobiology at the School of Earth and Ocean Sciences of Cardiff University. He received his PhD from the University of Oldenburg (Germany).

Henrik is a biogeochemist, geomicrobiologist and microbial physiologist with a special interest in anaerobic processes and the prokaryotes involved, such as the strictly anaerobic sulphate reducers and methanogens. He has been working on anaerobic metabolism and described new metabolic pathways in methanogens. One main topic of his research is life in the extreme environments, particularly life in the deep biosphere and in deep-sea anoxic brine lakes. These studies aim to reveal how anaerobes adapt to their particular ecological niches (e.g. oxygen tolerance of sulphate reducers). His work utilizes a range of different approaches including in situ activity measurements and the estimation of viable population sizes, but also culture-based laboratory experiments. Another aspect of his work has been the use of biomarkers, including dipicolinic acid for the detection of endospores in environmental samples.

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Introducing the Mathematical Modelling of Infectious Disease Dynamics Collection

In recent months, the words “infection” and “outbreak” have not been far from anyone’s mind as we’ve faced the emergence of a new coronavirus, COVID-19. Across the globe, efforts are underway to control and limit

Introducing the Mathematical Modelling of Infectious Disease Dynamics Collection

In recent months, the words “infection” and “outbreak” have not been far from anyone’s mind as we’ve faced the emergence of a new coronavirus, COVID-19. Across the globe, efforts are underway to control and limit the spread of the virus, and to find ways to treat those infected. As we watch these events unfurl, it is evident that there is still a lot that we, as a global community, do not yet understand about the dynamics of infectious diseases. The ways in which diseases spread are a concern that we all have a stake in?research that helps further our understanding of infectious diseases can influence each of our lives.

 

One distinct community of researchers working on understanding infectious disease dynamics is the mathematical modelling community, consisting of scientists from many different disciplines coming together to tackle a common problem through the use of mathematical models and computer simulations. Mathematics may sound like an unlikely hero to help us overcome a global epidemic; however, the insights we gain from studying the dynamics of infectious diseases by using equations describing fundamental variables are not to be underestimated. By approaching infectious diseases from a mathematical perspective, we can identify patterns and common systems in disease function, and it enables us to find some of the underlying structures that govern outbreaks and epidemics. Mathematical modellers make use of available data from current and previous outbreaks to predict who may get infected, where vaccination efforts will be most effective, and how to limit the spread of the disease.

 

Today at PLOS, we are launching a collection of new research papers submitted to a call for papers during the latter half of 2019 entitled “Mathematical Modelling of Infectious Disease Dynamics”, hosted by PLOS Biology, PLOS Computational Biology and PLOS ONE. The aim of this collection is to bring together different disciplines such as mathematics, biology, medicine and physics in order to shed light on the important topic of how mathematical models can help us understand infectious disease dynamics, and to present this research to the broad readership of these three journals and beyond. The accumulation of vital new research in a comprehensive collection will be a useful resource for understanding how infectious diseases operate, and how we can tackle them in real-time as well as in the future.

 

At PLOS we remain committed to our primary Open Access mission?ensuring that science is made as widely available as possible, and not locked behind paywalls. This is especially important in outbreak scenarios, such as the current COVID-19 epidemic, where it is critical that any new and relevant research be made easily accessible around the world, immediately at the time of publication.

Novel Coronavirus SARS-CoV-2 NIAID CC-BY

Several of the papers in this collection present new methods that can be utilized in a range of scenarios. For instance, Patel and Sprouge developed a new estimator for predicting the basic reproduction number R0, which is the expected number of host cells infected by a single infected cell. This can be used for instance to understand the early stages of HIV infections, and for assessing the effectiveness of various therapies.

 

If two pathogen species, strains, or clones don’t interact, surely we can estimate the proportion of coinfected hosts as the simple product of the individual prevalences? A paper in PLOS Biology by Frédéric Hamelin, Nik Cunniffe and co-workers shows that this assumption is false; even if pathogens don’t interact, death of coinfected hosts causes net prevalences of individual pathogens to decrease simultaneously. The authors reinterpret data from previous studies accordingly.

 

Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. In this PLOS Biology paper, Shirlee Wohl, Pardis Sabeti and co-authors paired epidemiological data from public health investigations with analysis of mumps virus whole-genome sequences from 201 infected individuals. This allowed them to reconstruct mumps transmission links not evident from more traditional approaches and also revealed connections between apparently unrelated mumps outbreaks.

 

Endo and colleagues present a model of a phenomenon to which we can all relate, but which is still not well understood – the spread of infection within the household. They modelled the fine structures of family life to understand how disease typically enters and spreads through the household. Their findings support the idea that children are the most likely culprits of bringing disease into the household, and showed that there is a high level of transmission within generations, as well as between mother and child.

FluShot NIAID CC-BY

Rotavirus, the leading cause of diarrhea globally in children under 5, shows a biennial pattern of emergence in the US, while in many other high-income countries it exhibits an annual pattern. Ai and colleagues modelled the effect that higher vaccine coverage may have on this phenomenon, and found that increasing vaccine coverage from the current 70-75% to 85% would not only reduce the number of rotavirus cases, but also shift occurance to a more predictable annual epidemic pattern.

 

Two of the papers published in the collection are concerned with malaria. Kim and colleagues modelled the effectiveness of relapse control methods for Plasmodium vivax, finding that current vector control methods may have a negative effect on controlling disease prevalence, but that a shift towards control at a higher vector control level may be more efficient. Meanwhile, Wang and colleagues have constructed a stacking model for malaria prediction by combining two traditional time series models and two deep learning methods. Utilising malaria incidence data from Yunnan Province, China, they find that the ensemble architecture outperforms each of the sub-structure models in predicting malaria cases.

Predicted dengue importations for August 2015 pone.0225193 CC-BY

There are two papers in the collection that look at improving prediction of dengue infections. Leibig and colleagues present a network model of how international air travel can affect the spread of dengue across the world. By modelling the number of dengue-infected passengers arriving at various airports each month, the authors were able to study how dengue may be imported into different countries, and which routes would be the most likely for dengue-infected passengers to arrive by. Secondly, Liu and colleagues developed a model for predicting the spread of dengue infections that incorporates climate factors such as mean temperature, relative humidity and precipitation and applied this to data from dengue infections in Guangzhou, China, in order to help inform best practices in the early stages of a dengue outbreak.

 

The development of diseases can be influenced by personal factors such as age, which two of the papers in the collection address. Ku and Dodd developed a model for accounting for population aging when looking at tuberculosis incidence, as the impact of demographic change on disease forecasting is still not well understood. They applied the model to historical data of TB cases in Taiwan from 2005-2018, and used this to forecast what the incidence may look like until 2035. On the other end of the age spectrum, Rostgaard and colleagues used a Markov model to study the relationship between Epstein-Barr virus and infectious mononucleosis. Most people are typically infected with Epstein-Barr virus in early childhood, while infectious mononucleosis can sometimes follow in adolescence or later in life. The authors developed a statistical model to probe some of the uncertainties surrounding the origin and dynamics of infectious mononucleosis.

 

Some of the papers in the collection address new and emerging diseases. Dodero-Rojas and colleagues used the SEIR model to study the last three Chikungunya outbreaks in Rio de Janeiro, Brazil, and estimated their respective Basic Reproduction Numbers, R0. They also expanded their findings to include predictions for the Mayaro virus, which is an emerging disease in South America, and found that it has the possibility to become an epidemic disease in Rio de Janeiro.

Aedes Mosquito NIAID CC-BY

The ability to accurately forecast disease patterns is crucial for ensuring that the right resources are in place to handle outbreaks. Morbey and colleagues looked at seasonal patterns in respiratory disease in England, and found that although syndromic indicators were affected by the timing of the peaks in seasonal disease, the demand for hospital beds was the highest on either 29th or 30th December, regardless of the timing of the syndromic peaks. Asadgol and colleagues also addressed seasonal patterns, this time in cholera in Iran, and predicted the effect of climate change on cholera incidence from 2020-2050 using an artificial neural network.

 

Given the interdisciplinary nature of the topic, we are grateful to countless authors, reviewers, Academic Editors and Guest Editors for making this collection a reality. We are especially grateful to our Guest Editor team, Konstantin Blyuss (University of Sussex), Sara Del Valle (Los Alamos National Laboratory), Jennifer Flegg (University of Melbourne), Louise Matthews (University of Glasgow) and Jane Heffernan (York University) for curating the collection. While 14 papers are included in this collection today, we’ll keep adding new papers as they are published, so please keep checking back for updates.

 

Guest Editor Konstantin Blyuss sums up the importance of this collection: “A recent and ongoing outbreak of coronavirus COVID-19 has highlighted the enormous significance of mathematical models for understanding the dynamics of infectious diseases and developing appropriate strategies for mitigating them. Mathematical models have helped identify the important factors affecting the spread of this infection both globally, and locally using country-specific information. They have also elucidated the effectiveness of different containment strategies and provided quantitative measures of disease severity”.

 

About the Guest Editors:

 

Konstantin Blyuss

Guest Editor, PLOS ONE, PLOS Biology, and PLOS Computational Biology

Konstantin Blyuss is a Reader in the Department of Mathematics at the University of Sussex, UK. He obtained his PhD in applied mathematics at the University of Surrey, which was followed by PostDocs at Universities of Exeter and Oxford. Before coming to Sussex in 2010, he was a Lecturer in Complexity at the University of Bristol. His main research interests are in the area of dynamical systems applied to biology, with particular interest in modelling various aspects of epidemiology, dynamics of immune responses and autoimmunity, as well as understanding mechanisms of interactions between plants and their pathogens

 

Sara del Valle

Guest Editor, PLOS ONE, PLOS Biology, and PLOS Computational Biology

Dr. Sara Del Valle is a scientist and deputy group leader in the Information Systems and Modeling Group at Los Alamos National Laboratory. She earned her Ph.D. in Applied Mathematics and Computational Science in 2005 from the University of Iowa. She works on developing, integrating, and analyzing mathematical, computational, and statistical models for the spread of infectious diseases such as smallpox, anthrax, HIV, influenza, malaria, Zika, Chikungunya, dengue, and Ebola. Most recently, she has been investigating the role of heterogeneous data streams such as satellite imagery, Internet data, and climate on detecting, monitoring, and forecasting diseases around the globe. Her research has generated new insights on the impact of behavioral changes on diseases spread as well as the role of non-traditional data streams on disease forecasting.

 

Jennifer Flegg

Guest Editor, PLOS ONE, PLOS Biology, and PLOS Computational Biology

Jennifer Flegg is a Senior Lecturer and DECRA fellow in the School of Mathematics and Statistics at the University of Melbourne. Her research focuses on mathematical biology in areas such as wound healing, tumour growth and epidemiology. She was awarded a PhD in 2009 from Queensland University of Technology on mathematical modelling of tissue repair. From 2010 – 2013, she was at the University of Oxford developing statistical models for the spread of resistance to antimalarial drugs. From 2014 – April 2017 she was a Lecturer in the School of Mathematical Sciences at Monash University. In May 2017 she joined the School of Mathematics and Statistics at the University of Melbourne as a Senior Lecturer in Applied Mathematics.

 

Louise Matthews

Guest Editor, PLOS ONE, PLOS Biology, and PLOS Computational Biology

Louise Matthews is Professor of Mathematical Biology and Infectious Disease Ecology at the Institute of Biodiversity, Animal Health and Comparative Medicine (BAHCM) at the University of Glasgow. She holds a degree and PhD in mathematics and has over 20 years research experience as an epidemiologist, with a particular focus on diseases of veterinary and zoonotic importance. Her current interests include a focus on drug resistance; antibiotic resistance in livestock; the community and the healthcare setting; anthelminthic resistance in livestock; and drug resistance in African Animal Trypanosomiasis. She is also interested in the integration of economic and epidemiological approaches such as game theory to understand farmer behaviour and micro-costing approaches to promote adoption of measures to reduce antibiotic resistance.

Jane Heffernan

Guest Editor, PLOS ONE, PLOS Biology, and PLOS Computational Biology

Jane Heffernan is a Professor in the Department of Mathematics and Statistics at York University, and York Research Chair (Tier II). She is also the Director of the Centre for Disease Modelling (CDM), and serves on the Board of Directors of the Canadian Applied and Industrial Mathematics Society (CAIMS). She is also very active in the Society for Mathematical Biology (SMB). Dr. Heffernan’s research program centers on understanding the spread and persistence of infectious diseases. Her Modelling Infection and Immunity Lab focuses on the development of new biologically motivated models of infectious diseases (deterministic and stochastic) that describe pathogen dynamics in-host (mathematical immunology) and in a population of hosts (mathematical epidemiology), as well as models in immuno-epidemiology, which integrate the in-host dynamics with population level models. More recently, Heffernan is focusing on applying mathematics and modelling to studying pollinator health and disease biology.

 

 

 

Featured Image : Spencer J. Fox, CC0

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Introducing PLOS ONE’s Science of Stories Collection

Stories have the power to shape our identities and worldviews. They can be factual or fictional, text-based or visual and can take many forms—from novels and non-fiction to conspiracy theories, rumors and disinformation. We can characterize stories by their plot, their characters, their audience, their style, their themes or their purpose. Given the massive power of stories to alter the course of society, innovative methods to understand them empirically and quantitatively are necessary.

Today, we are pleased to introduce PLOS ONE’s Science of Stories Collection, which  includes submissions invited through a Call for Papers last year. The Call for Papers welcomed primary research papers that propose solutions to real world, data-rich problems that use different empirical methods. The Guest Editors overseeing the scope and curating the Collection are Peter Dodds (University of Vermont), Mirta Galesic (Santa Fe Institute), Matthew Jockers (Washington State University), and Mohit Iyyer (University of Massachusetts Amherst).

At launch, the Collection includes over 15 papers illustrating data-driven approaches to understanding stories and their impact. Some articles explore the nature of narrative and narrative thinking in texts and other media, for instance, the role of similarity in narrative persuasion, the effects of choosing violence in narratives, the importance of characters in narratives communicating risk of natural disaster, the impact of storytelling in complex collaborative tasks such as food preparation, and the role of narrative in collaborative reasoning and intelligence analysis.

Other articles present new methods to extract stories from datasets and datasets from stories, including automated narrative analysis via machine learning, systematic modeling of narrative structure and dynamics, and large-scale analysis of gender stereotypes in movies and books.

A third group of papers analyze how narratives are transformed and how they can transform people, for example, looking at the co-evolution of contagion (e.g., disease, addiction, or rumor) and behavior, social media’s contribution to political misperceptions in US elections, how people’s intuitive theories of physics can partly account for how they think about imaginary worlds, how narrative can induce empathy for people engaging in negative health behaviors, and the impact of mental health recovery narratives on health outcomes.

A final group of papers explores the communication of data-rich narratives to the public, including the relative effectiveness of video abstracts and plain language summaries versus graphical abstracts and published abstracts, newly emerging platforms for writing and commenting on literary texts at unprecedented scale, and the role of narrative in perceived authenticity in science communication.

Papers will continue to be added to the Collection as they reach publication, so we invite you to revisit the Collection again for additional insights into the science of stories.

Guest Editors

Peter Sheridan Dodds

Peter Dodds is Professor at the University of Vermont’s Department of Mathematics and Statistics. He is Director of the Vermont Complex Systems Center and co-runs the center’s Computational Story Lab. Having a general interest in stories and narratives, complexification, contagion, and robustness, Dodd’s research focuses on system-level, big data problems of all kinds, often networked, sociotechnical ones. His work has been supported by an NSF CAREER award to study sociotechnical phenomena, the McDonnell Foundation, the Office of Naval Research, NASA, the MITRE Corporation, Computer Associates, and Mass Mutual.

Mirta Galesic

Mirta Galesic is Professor and Cowan Chair in Human Social Dynamics at the Santa Fe Institute, External Faculty at the Complexity Science Hub in Vienna, Austria, and Associate Researcher at the Harding Center for Risk Literacy at the Max Planck Institute for Human Development in Berlin, Germany. She studies how simple cognitive mechanisms interact with social and physical environments to produce seemingly complex social phenomena. She develops empirically grounded computational models of social judgments, social learning, collective problem solving, and opinion dynamics. She is also interested in how people understand and cope with uncertainty and complexity inherent in many everyday decisions.

Mohit Iyyer

Mohit Iyyer is an Assistant Professor in computer science at the University of Massachusetts, Amherst. Previously, he was a Young Investigator at the Allen Institute for Artificial Intelligence. Mohit obtained his PhD at the University of Maryland, College Park, advised by Jordan Boyd-Graber and Hal Daumé III. His research interests lie in natural language processing and machine learning. Much of his work uses deep learning to model language at the discourse level, tackling problems like generating long coherent units of text, answering questions about documents and understanding narratives in fictional text.

Matthew L. Jockers

Matthew L. Jockers is Dean of the College of Arts & Sciences and Professor of English and Data Analytics at Washington State University in Pullman, WA. Jockers has been leveraging computation to understand narrative and style since the early 1990s.  His books on the subject include Macroanalysis: Digital Methods and Literary History, Text Analysis with R for Students of Literature, and The Bestseller Code.  In addition to his academic work, Jockers helped launch two text mining startups and worked as Principal Research Scientist and Software Development Engineer in iBooks at Apple.

 

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It’s the little things- An interview with the Guest Editors of our Microbial Ecology of Changing Environments Call for Papers

PLOS ONE has an open Call for Papers on the Microbial Ecology of Changing Environments, with selected submissions to be featured in an upcoming Collection. We aim to highlight a range of interdisciplinary articles showcasing

It’s the little things- An interview with the Guest Editors of our Microbial Ecology of Changing Environments Call for Papers

PLOS ONE has an open Call for Papers on the Microbial Ecology of Changing Environments, with selected submissions to be featured in an upcoming Collection. We aim to highlight a range of interdisciplinary articles showcasing the diversity of systems, scales, interactions and applications in this dynamic field of research.

We spoke to the Guest Editors for this project, Melissa Cregger and Stephanie Kivlin, about what motivates their research and the challenges and opportunities faced by microbial ecologists.

 

What makes microbes so interesting?

MC: Microorganisms are everywhere and are important members of all of the ecosystems they inhabit. There are microorganisms in soils, oceans, lakes, and even within our bodies. Within all of these habitats they are performing really important functions. In lakes, oceans, and soils, microorganisms are key to moving nutrients around. Within our bodies, they aid in things like digestion and disease prevention.

SK: Microorganisms are fascinating in how genetically diverse and numerous they are. Microorganisms can be found in almost every habitat on Earth and are often the first to respond to environmental disturbance and global change. Thus, microorganisms likely hold the key to solving most of Earth’s problems as we face global climate change.

 

How is microbial ecology relevant to major environmental and societal issues like climate change and food security?

MC: Given how ubiquitous microorganisms are across the world, understanding how they function is key if we want to understand and mitigate the consequences of climatic change and if we want to grow food more sustainably and in marginal lands. For instance, if we can get a better understanding of microbial carbon cycling, we can potentially use biological carbon capture as a mitigation strategy to help combat rising levels of atmospheric carbon dioxide. Additionally, researchers around the world are trying to understand how plants interact with microbial communities in an effort to harness these microbes to increase food production and the ability of plants to withstand changing abiotic conditions.

SK: Microorganisms are the key for innovating nature-based solutions to climate change. For example, specific fungal symbionts of plants can be tailored to increase agricultural plant drought tolerance. Other microorganisms may be deployed to remediate oil spills or other man-made pollutants. Finally, engineering plant-microbial associations may lead to a larger terrestrial carbon sink to offset atmospheric CO2 concentrations, creating a negative feedback to climate change itself.

 

Tell us a bit about your own research and how it ties in with some of these issues.

MC:  A large portion of my research is focused on understanding how to use beneficial microbes to increase plant productivity and tolerance to drought, and also in understanding how these communities function in the soil environment with the ultimate goal of using them to enhance ecosystem stability. I am part of two large multi-disciplinary teams at Oak Ridge National Laboratory that are specifically focused on plant-microbe interactions in the potential biofuel feedstock, Populus. We are trying to characterize basic principles governing plant-microbe interactions in the hope of making Populus a better biofuel that can grow in marginal lands with limited input of fertilizer and water.

SK: Research in the Kivlin Lab aims to create distribution models for terrestrial microorganisms and their functions. Our current focus is on arbuscular mycorrhizal (AM) fungi, as these plant symbionts are the main providers of nutrients and drought tolerance to agricultural plants. We are interested in where these fungi are, the ecosystem-level carbon and nutrient cycling they promote and how sensitive these plant-fungal interactions may be to climate change. To address these questions, we both compile data on AM fungal distributions worldwide, but also examine plant-AM fungal interactions along altitudinal gradients that serve as a space for time substitution for climate change and in long-term climate change experiments.

 

How are technological advances opening up new opportunities in your field?

MC: Over the last 20 years there have been rapid advances in sequencing and molecular techniques that have enabled amazing opportunities in microbial and ecosystem ecology. We are finally able to identify unculturable microorganisms inhabiting diverse communities using next generation sequencing and are getting clues into their function using metagenomics, metatranscriptomics, proteomics, and metabolomics. Further, using these techniques, people are developing some new strategies to culture more microbes.

SK: It is increasingly clear that the genomics revolution has impacted microbial ecology. We now can link functional genetic potential to microorganisms in environmental microbiomes and understand how interactions among microorganisms and between microorganisms and plants control expression of these functional genes and the metabolites they code for.

 

How does microbial ecology benefit from interdisciplinary collaboration?

MC: Microbial communities are incredibly complex, therefore understanding their role in ecosystems really requires a systems biology approach. Because of this, having an interdisciplinary team to tackle questions at various scales is really important.

SK: Microbial ecology is inherently interdisciplinary. We collaborate with earth system modelers to scale microbial function from the organism to the globe and with geneticists to understand the genetic underpinnings of those functions. Without these collaborations, our field would be siloed to case-studies of microbial communities and lack the ability to develop first-principles theory across microbial communities and environments.

 

What are some of the biggest unsolved questions in microbial ecology?

MC: There are so many unsolved questions in microbial ecology that it is hard to just identify a few. We still have a limited understanding of how microbial communities fluctuate through time. How stable are they within ecosystems? Are organisms within communities functionally redundant? Does this redundancy aid in resilience of the community post disturbance? How do these communities respond to fluctuations in abiotic variables? I could really go on and on.

SK: Despite all of the vital roles that microorganisms provide in the environment, we still don’t understand (1) where microorganisms even are spatially and what abiotic and biotic processes control these distributions, or (2) how temporally dynamic microbial communities are both within and among plant growing seasons. Answering these fundamental questions will allow us to understand linkages between microbial communities and plant growth, microbial composition and ecosystem carbon and nutrient cycles, and allow us to effectively manipulate microbial consortia for societal gain in agricultural and bioremediation settings.

 

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