Infectious disease modeling in a time of COVID-19 – PLOS ONE authors’ perspectives

In February 2020, PLOS published a Collection entitled “Mathematical Modeling of Infectious Disease Dynamics” which includes papers from PLOS ONE, PLOS Biology and PLOS Computational Biology, on a variety of topics relevant to the modeling of infectious disease, such as disease spread, vaccination strategies and parameter estimation. As the world grappled with the effects of COVID-19 this year, the importance of accurate infectious disease modeling has become apparent. We therefore invited a few authors  featured in the Collection to give their perspectives on their research during this global pandemic. We caught up with Verrah Otiende (independent researcher, Pan African University Institute of Basic Sciences Technology and Innovation), Lauren White (USAID), Jess Liebig (CSIRO) and Johnny Whitman (The Ohio State University) to hear their reflections on this collection and the time that has passed.

In this first blog post of a set of two, we hear from Verrah Otiende and Lauren White, who discuss the modeling of other infectious diseases such as HIV and TB during the COVID-19 pandemic, the importance of good data, the increasing focus of incorporating human behavior in disease models, and more. Please check back in a couple of weeks for the next installment of this blog post series.

What is your research focused on currently?

VO: Currently, I am independently researching the spatiotemporal patterns of successful TB treatment outcomes for HIV co-infected cases in Kenya. The motivation of this study is mainly the convergence of TB and HIV epidemics that threatens the management of TB treatment. This is evidenced by various spatial studies that have described how HIV co-infection propagates unsuccessful TB treatment outcomes. I am using the Bayesian Hierarchical Modeling approach to generate the estimates for each of the 47 counties of Kenya. These estimates will help identify the high-risk counties with successful TB treatment outcomes and deliberately prioritize other counties with an increased risk of unsuccessful treatment outcomes.

I believe that we will continue to improve disease models as we learn more about the ways that individual contact patterns, behaviors, and immune responses affect epidemics.

Lauren White

LW: I am a quantitative disease ecologist interested in developing and improving mathematical models of disease to assist in prediction and prevention of emerging and zoonotic infectious diseases in the context of rapidly changing, human-impacted environments. The overall objective of my research is to explore the effects of heterogeneity in behavioral and immune competence on disease modeling predictions within and across populations. I use mathematical modelling approaches, integrated with empirical data, to explore three different types of heterogeneity that can alter individual transmission rates: (i) within-host heterogeneity; (ii) contact heterogeneity and group structure within populations; and (iii) spatial heterogeneity across landscapes. My work also has broader implications for understanding human disease risk within the One Health framework, which includes human, animal, and environmental health.

What do you think are the lessons we can learn from the research in your field which will help us to better model infectious diseases in the future?

VO: Applying Bayesian algorithms to modeling multiple related infectious diseases is critical for quantifying both the joint and disease-specific risk estimates. The flexibility and informative outputs of Bayesian Hierarchical Models play a key role in clustering the geographical risk areas over a given time period. This would further provide additional insights towards the collaborative monitoring of the diseases and facilitate the comparative benefit obtained across the disease populations.

LW: Before this year, “superspreader” was considered a technical term, but COVID-19 has really highlighted the role of individual behavior in community spread.  I believe that we will continue to improve disease models as we learn more about the ways that individual contact patterns, behaviors, and immune responses affect epidemics. These are still very open questions, especially for less-studied livestock and wildlife, host-pathogen systems.

It is critical not to ignore other life-threatening infectious diseases while working towards managing COVID-19.

Verrah Otiende

Have your motivations, direction or the way you conduct or disseminate your research changed in 2020 as a consequence of the COVID-19 pandemic, either for yourself or the field as a whole?

VO: I am still enthusiastic about conducting and disseminating research work on infectious diseases. The direction has changed as a consequence of the COVID-19 pandemic, especially during dissemination. But the most positive effect of this change was reaching a wider audience virtually than I have ever thought of.

On case notifications, my worry is on underreporting and data capture processes of other infectious diseases since most efforts have been directed towards controlling and preventing the spread of COVID-19. Probably the non-pharmaceutical practices like physical distancing and lockdowns have kept some infectious diseases from spreading for now but there is still a vacuum for certain diseases to rebound and spread which could have much more severe consequences to millions of humans for a very long time. It is critical not to ignore other life-threatening infectious diseases while working towards managing COVID-19.

LW: I have just recently started a position through the AAAS Science and Technology Policy Fellowship program. This means that I am spending less time researching questions around COVID-19 directly but learning a lot more about program planning and implementation, as well as the effects of COVID-19 on other public health efforts like epidemic control for HIV/AIDS. This is an important career opportunity for me to see what makes science actionable and useful for stakeholders, policymakers, and other end users.

Disease models are only as good as the information or data that we put into them—often times in new situations we end up using “best guesses.”

Lauren White

If there was one thing you wished that the general public understood better about modeling infectious diseases, what would that be?

VO: Modeling the joint dynamics of infectious diseases and human behavior is fundamental in understanding and quantifying the risks and effects associated with their global spread.

LW: COVID-19 has highlighted some confusion in how disease models are used for decision making. Disease models come in many types, but especially those that aim to predict or forecast the future function as thought experiments, not as written-in-stone prophecies. Disease models are only as good as the information or data that we put into them—often times in new situations we end up using “best guesses.” As our information and estimates improve, so can the accuracy of our models. This is not, by default, bad science; it simply reflects an iterative process.

It is also important to note that sometimes models can show as the worst case or “do nothing” scenario. Again, such an outcome is not a forgone conclusion. Public health interventions can help us do better. So better outcomes are not necessarily a failure of modeling or an overreaction to an epidemic, rather they are an indication that we, as a society, are doing something right.

Are there any unanswered research questions in this field that you would really like to see us make progress on?

VO: Numerous unanswered research questions would be of interest to progress on. A quick one that comes to my mind would be incorporating human behavior in the spatiotemporal joint modeling of infectious diseases to understand the possible effects of such behavior. This would require rich behavioural datasets and developing unsupervised ML algorithms to automate and predict the risks of joint infections over spatial and temporal dimensions.

LW: There will always be more to discover with regards to infectious diseases, but I actually think that the most pressing question is how we, as a scientific community, will do a better job in this current crisis and during future epidemics. I have faith that we will be able to answer research questions as they arise, and in fact, we have increased our understanding of a completely novel pathogen incredibly quickly. But we need to think more critically about how we are communicating results and making our work actionable: How do we maintain and build trust in a climate where scientific expertise itself is controversial? How can we better engage with the communities that we live in and serve? Are we communicating results thoughtfully and responsibly? These are by no means “new” or “novel” research questions, but COVID-19 has starkly highlighted their importance. 

About the authors:


Verrah Otiende: My name is Verrah Otiende and I am a statistician and an ML enthusiast with proven expertise in data governance concepts and using Big Data platforms to efficiently store and manage large amounts of data. I am an independent researcher and currently working on building, evaluating, and integrating predictive models on infectious disease case notifications using unsupervised ML algorithms to optimize intervention options and public health decisions. Besides infectious disease modeling, I am also working on the Named Entity Recognition (NER) datasets to build translation models for African languages through the MASAKHANE research initiative for Natural Language Processing (NLP).


Lauren White: Dr. Lauren White is a first year AAAS Science and Technology Policy Fellow at the Office of HIV/AIDS in USAID. Dr. White has a background in infectious disease modeling and epidemiology with an interest in the intersections of human, animal, and environmental health. Most recently, she worked as a post-doctoral research fellow at the National Socio-Environmental Synthesis Center (SESYNC) at the University of Maryland. Dr. White finished her Ph.D. in 2018 at the University of Minnesota in the Department of Ecology, Evolution & Behavior.

Disclaimer: Views expressed by contributors are solely those of individual contributors, and not necessarily those of PLOS.

Disclaimer from Lauren White: The views in this interview are those of the author and do not necessarily represent the views of USAID, PEPFAR, or the United States Government.

Featured Image : Spencer J. Fox, CC0

The post Infectious disease modeling in a time of COVID-19 – PLOS ONE authors’ perspectives appeared first on EveryONE.

A river of new ecological data – An Interview with the Guest Editors of our Freshwater Ecosystems Call for Papers

Freshwater ecosystems provide important services to human societies, such as water, food, regulation of hydrological extremes, pollutant attenuation, and carbon sequestration. As freshwater systems are under pressure from human activity and climate change, a more complete understanding of these systems is needed to respond to the environmental changes associated with these processes.

Here Prof Kirsten Seestern Christoffersen and Dr Ben Abbott, Guest Editors of PLOS ONE Call for Papers on Freshwater Ecosystems, share their thoughts on the present and future of freshwater science research.

What are the most interesting scientific advances in freshwater science recently?

KSC: I would say it is the enormous amount of data that is becoming available as we apply more and more continuous recording data loggers with sensitive sensors, drones, unmanned vehicles, all sort of cameras, fast running analytic instruments – and that these great things are also becoming more and more affordable. Because of these advances, it is possible to get data, photos and live videos for almost any part of the World, from the deepest lakes and the permanently ice-covered lakes to boiling mud-holes. And then, it follows from these advances mentioned above that these great challenges require computer power to handle, analyse and store these large amounts of data. So, it is no longer a question of how to get enough data but rather how to manage the wealth of data that we can produce.

BA: Our capacity to measure parameters in more ways has greatly expanded over the past two decades. This opens up the possibility for new spatiotemporal analyses to move beyond just calculating concentrations and loads to understanding the mechanisms driving ecosystem function across the terrestrial-aquatic gradient. The combination of traditional physicochemical parameters with metrics of ecological community and remotely-sensed watershed characteristics is really exciting.

And, on the other hand, what are the main challenges freshwater ecosystems will face in the near future?

KSC: Here I would say all the “usual challenges”: climate change, biodiversity crisis, eutrophication (still an issue despite it has been a problem for many years now). One thing that we really need to do is to establish what the baseline conditions are especially for freshwater ecosystems that have not yet been affected too much – like the freshwaters in the Arctic and alpine regions.

BA: This flood of new data represents a challenge in itself. More numbers do not automatically translate into greater understanding. We need new approaches to extract meaningful patterns and attribute those signals to ecological processes, especially human disturbance. Another challenge is that many of our long-term monitoring stations are at risk because of changes in funding priorities. We need to leverage these long-term data sources and figure out ways to better integrate across sites.

What new approaches are needed to respond to these challenges?

KSC: Awareness, political will and resources.

BA: See my last two responses.

What are your main research interests? What do you consider to be your biggest accomplishment in your career so far?

KSC: My main interests these years are understanding how Arctic freshwater ecosystems are organised under different (natural) environmental conditions and identifying the drivers and stressors that rule the biota. This might be the key elements to understand the uniqueness of pristine ecosystems and also to be able to predict their changes.

BA: There are still two million people who die every year from polluted water. Many more than that are affected by chronic or acute disease associated with exposure to pollutants. At the same time, aquatic ecosystems around the world are experiencing huge declines in biomass and biodiversity. We need to improve global water governance and ensure access to clean water for all people and ecosystems. The biggest accomplishment of my career has been the privilege of working with students, researchers, and water managers who are striving to address these global water crises.

What advice would you give to early-career freshwater researchers that want to make a difference?

KSC: It will be to follow your interests and go for the things that you think is important; if you can’t really get yourself into an enthusiastic mode when doing your research, you should maybe change horse. In other words, don’t necessary follow the main stream and where the money is often good – but follow your sense for what really matters. Another go advice is to talk with other scientists but not only those that are close to you (physically and thematically)!

BA: The distinction between basic and applied research is really counterproductive. Any good research has applications, and we should be seeking to share the relevant information we discover with all interested parties. As an early-career researcher myself, I frequently ask myself, how relevant and important is the work I am doing? Are there other issues or problems that I could be contributing to in a meaningful way? In this time of accelerating consumption and restructuring of human activity, the world needs high-quality information more than ever.

***

PLOS ONE has an open Call for Papers on Freshwater Ecosystems. Researchers working on freshwater ecology are encouraged to submit their work before January 8, 2021.

***

About our Guest Editors:


Kirsten Seestern Christoffersen

Kirsten Seestern Christoffersen is Professor of Freshwater Ecology at the University of Copenhagen


Ben Abbott

Ben Abbott is an Assistant Professor at Brigham Young University

The post A river of new ecological data – An Interview with the Guest Editors of our Freshwater Ecosystems Call for Papers appeared first on EveryONE.

Open science and cognitive psychology: An interview with Guest Editor Nivedita Mani and Mariella Paul

Nivi is Professor at University of Göttingen, Germany where she leads the “Psychology of Language” research group at the Georg-Elias-Müller Institute for Psychology. Her work examines the factors underlying word learning and recognition in young children and views word learning as the result of a dynamic mutual interaction between the environment and the learner. She is also one of the Guest Editors of an ongoing PLOS ONE Call for Papers in developmental cognitive psychology in collaboration with the Center for Open Science. This Call has a particular emphasis on reproducibility, transparency in reporting, and pre-registration.


Prof. Dr. Nivedita Mani

Mariella is a postdoctoral researcher in Nivi’s department. She is interested in how children’s interests shape their word learning, which she investigates using several methods, including EEG, online studies, and meta-analytic approaches. Mariella was one of the co-founders of the Open Science initiative at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, where she did her PhD, and was awarded an eLife Community Ambassadorship to promote open science.


Mariella Paul

I asked them about their views on how open science affects and shapes their research and their field.

Can you tell me about your interest in open science?

MP: The first time I heard about open science and the replication crisis was during a conference I attended during my Master’s, but I only really got into it during my PhD, when I learned much more about it through academic Twitter and started to apply it to my own research. I think the ideas around open science appealed to me as a (then very) early career researcher (ECR) because they were how I, perhaps idealistically, thought science should be done. I have heard the same sentiment from bachelor’s (or undergrad) students when giving lectures about open science practices: “Why wasn’t it always done like this?”. After learning bits and pieces from Twitter and podcasts, such as ReproducibiliTea and the Black Goat, I got in touch with other ECRs at my institute and we founded an open science initiative, organized workshops for our colleagues and ourselves to learn more about open science, and eventually even started our own ReproducibiliTea journal club, where we read and discuss papers about different open science practices.

NM: My interest in open science is relatively recent. I am quite late to the party and my invitation is by virtue of the people in my lab who keep finding better ways to do science. My interest is driven by the fact that the small steps towards transparency and best practice that we take in successive projects not only makes us more confident of the results we report but also makes us calmer in planning projects. What I find interesting and quite marvelous actually, is that this trend towards greater transparency in research and reporting is being spearheaded by young researchers. That’s really amazing to me, because, as a tenured Professor, that next publication – and lingering difficulties associated with publishing null results – is not going to impact my next paycheck but it might well impact the future prospects of the young researchers who are leading this change, who nevertheless weigh doing science well equally with getting cool results!    

How does transparency in reporting affect your own research?

MP: My PhD consisted largely of conceptual replications, that is, I replicated studies previously done with infants and adults with young children. Directly building on previous studies has clearly illustrated the need for transparent reporting for me – because only with transparent reporting and shared materials one can hope to conduct a close replication. Therefore, for my own research, I aim to report my methods as transparently as possible, to make the lives of future researchers wanting to run replications or meta-analyses easier.


Photo by Markus Spiske on Unsplash

NM: I think the best thing to say for it is that it is frees you. There is, on the one hand, more acceptance these days for the publication of null results, but also, more importantly, greater appreciation for the scientific process rather than the scientific result. This makes it a much more relaxing climate to be a researcher in, since you don’t need to find that perfect result, you need only to document that you went about looking for evidence of that effect in an appropriate manner. This makes you more conscious of critically evaluating your methods prior to testing while leaving you rather calm about the result of your manipulation. So for instance in my group, we now routinely write up the Introduction, Methods and Planned analyses of a paper before we start testing. This makes us think much more about what it is we are actually testing, what we plan to analyze, whether we can conduct the analyses we hope to, and whether that analyses actually tests the hypotheses under consideration. I think this way of planning studies not only makes us methodologically rigorous but also makes us more likely to actually find meaningful effects.

Why do you think pre-registration matters in developmental cognitive psychology?

MP: I think pre-registration can be valuable for any confirmatory study, by adding transparency early during the research process, and by decreasing researchers’ analytic flexibility. In developmental cognitive psychology in particular, we deal with unique issues. For example, when working with infants and young children, data collection and drop-outs require special attention. Pre-registration can help us set some of the parameters around these issues beforehand, for example by pre-specifying transparent data-peeking and planning a correction for sequential testing. I work a lot with EEG, where we additionally have a myriad of analytic decisions to make in how to preprocess the data. Also here, pre-registration can decrease researchers’ analytic flexibility and reduce bias by making these decisions before seeing the data.

NM: Developmental research is plagued with many of the issues in cognitive science, unfortunately amplified by difficulties with regards to access to participant pools (babies are more difficult to recruit relative to undergraduate students) and resulting issues in sample size, shorter attention spans of participants (leading to shorter and less well-powered experiments) as well as greater variance in infant responding. Thinking more carefully about the study and what you actually have adequate power to do – as one is forced to with a preregistration – may help us avoid costly mistakes of running under-powered studies that eventually lead to inconclusive results. From a pragmatic point of view, preregistration, in particular, helps us to better motivate analyses choices that may be questioned later in the process – so in a recent review of a paper, we were asked why we chose a particular exclusion criterion. We did not preregister this analysis (it’s a relatively old study that is only now seeing the light of day) but based this exclusion criterion on previous work – had we preregistered this, it would have been easier for us to justify our choice of this particular exclusion criterion. As it stands now, I can see that a skeptical reviewer may be inclined to believe our choice of this exclusion criterion is post-hoc.

How does the field of developmental cognitive psychology differ now compared to 10-15 years ago, and has open science played a role in that?

MP: I have only been in the field for a few years, but even in that time, I think open science has played a role in the development of the field. For example, large-scale replication efforts such as the ManyBabies project help us better understand central findings in our field, such as infants’ preference for speech presented in a child-directed manner. Similarly, platforms such as Wordbank – an open database of children’s vocabulary – and MetaLab –an interactive tool for meta-analysis in cognitive development – are now available for everyone to run their own studies on large-scale data.

there is greater acceptance of such “failed” experiments these days and this is to a large extent due to our increased appreciation for the scientific process (including open science practices) rather than the result.

NM: To be really honest, on a personal level, I am rather shamefaced about the practices that I believed acceptable 10 years ago. For instance, 10 years ago, I posted on social media that my “failed” experiments folder was 1.5 times larger than my “successful” experiments folder. Back then, it didn’t occur to me that the failed experiments folder (null results to be precise) was as important as the published successful experiments folder – and indeed, they were not failures, because they were providing us valuable information about potential contexts in which we do not find evidence for particular effects. However, now, there is greater acceptance of such “failed” experiments these days and this is to a large extent due to our increased appreciation for the scientific process (including open science practices) rather than the result. At the same time, there is greater emphasis on correct reporting of results, which I belatedly realize, I have been on the wrong side of, by not reporting aspects of the analyses that were important to interpretation of the results. I think this is changing too, with greater awareness of what we need to report when it comes to reporting the analyses we perform.  

What do you see as the greatest challenges for the field going forward?

MP: I think with the current development of the field and psychology in general, there are many challenges as well as opportunities. For many, including myself, one of the most direct challenges recently has been the restrictions on data collection due to the pandemic. With studies in the lab, as we know them, not having been possible (or only to a very limited degree) for over half a year now, many projects needed to be delayed, and we have been forced to rethink our way of planning new experiments. However, this unique situation also offers the possibility to conduct studies that we perhaps usually would not have thought of. For example, meta-analyses of previous studies in the literature can be conducted even when the lab is closed, and so can online-studies, of course. Also, the time away from the lab can be used to get started on new open science practices. For example, a registered report can be written and submitted so that the stage 1 protocol [i.e., a Registered Report Protocol at PLOS ONE] is already accepted by the time testing can be resumed.

NM: We seem to have achieved greater understanding of the requirements of good science, but I do worry about the extent to which we can implement these requirements. How can we run well-powered studies in developmental research, given restrictions on access to population pools and infant attention span? Cross-laboratory efforts (like the ManyBabies projects or a recent project on the effect of the Covid-19 lockdown on language development that I am involved in) here may be the way forward, allowing us to pool resources across laboratories. Equally, we are looking more deeply into sequential Bayesian designs, that may potentially allow us to get around some of the problems I have mentioned (sample size, power, inconclusive results). In general, I think we need to get more inventive about how to continue doing good developmental research.

At the same time, I don’t know if we really know how to analyze our data. In asking the more critical questions that the field is asking these days, I don’t really see one correct answer – and unfortunately, I don’t feel qualified to choose one answer over another. Again, I think greater transparency in research reporting helps here, because I get to post my data and my analyses and the results that I obtained with these analyses. This allows someone else to look through my data and analyze it differently to see if the pattern holds. Having said that, I don’t also think we are where we could be with regards to this solution – at least, I know my group isn’t – with regards to how well we archive our data and how transparent it is for others to use. That is definitely going to be one of the challenges we will face going forward.

The post Open science and cognitive psychology: An interview with Guest Editor Nivedita Mani and Mariella Paul appeared first on EveryONE.

Physical forces at the interface with biology and chemistry: a conversation with Kerstin Blank and Matthew Harrington

 

Cell behaviour, tissue formation/regulation, physiology and disease are all influenced by cellular mechanics and physical forces. The field of mechanobiology has for a long time striven to fully understand how these forces affect biological and cellular processes, as well as developing new analytical techniques. At the same time, the properties of advanced smart materials, such as self-healing, self-reporting and responsive polymers, have been determined by a complex interplay between the thermodynamics, kinetics and mechanics of dynamic bonding strategies. These are tightly connected to the field of mechanochemistry, which aims to elucidate and harness molecular level design principles and translate these to the bulk material level as emergent properties. At this interface between disciplines lies an emerging and exciting research area that has been strongly facilitated by the collaboration of physicists, chemists, engineers, materials scientists, and biologists.

We had the pleasure of speaking to Kerstin Blank and Matthew Harrington, who have been working on how mechanical forces influence biological systems, molecules and responsive biomaterials, about their views of the field and the recent ‘Multiscale Mechanochemistry and Mechanobiology’ conference of which PLOS ONE was one of the proud sponsors.

 

How did you first become interested in this topic?

 

Kerstin: When I started in this field in 2000, I was mostly impressed by the technical possibilities. I was working with Hermann Gaub, one of the leaders in single-molecule force spectroscopy. I found it fascinating that we could stretch a single biological molecule and observe its response. I did ask myself sometimes if this was just something that physicists like to play with or if one could solve biomedically relevant questions with this approach. Now, almost 20 years later, it has become very evident that a large number of biological systems are regulated by mechanical forces in many different ways.

 

Matt: My educational background was primarily in biology and biochemistry, but I became fascinated with the capacity of certain biological materials to exhibit self-healing responses in the absence of living cells. I reasoned that this must arise from specific chemical and physical design principles in the material building blocks themselves, and I became obsessed with figuring out how this works. This led me to the self-healing materials community, which was largely populated with chemists and materials engineers, but not so many biologists. When I began to see that many of the same principles at play in synthetic self-healing materials were present in nature, and that in some cases nature was going well beyond the state of the art in synthetic self-healing materials, I realized the enormous potential at the interface of mechanobiology and mechanochemistry. I haven’t looked back since.

 

Which areas are you most excited about?

 

Kerstin: I find it very intriguing how cells utilize mechanical information from their environment and then feed it into intracellular biochemical signalling cascades. Understanding these mechanosensing and mechanotransduction processes requires knowledge of the cellular players and their interactions. But to develop the complete picture, we also need to investigate how cells interact with their extracellular environment. This also involves understanding the microscopic and macroscopic mechanical properties of the extracellular environment. I am highly excited about the development of molecular force sensors that convert mechanical force into a fluorescent signal. This allows for the localized detection of cell traction forces and, in the future, will also enable us to visualize force propagation inside materials that mimic the natural extracellular matrix.

 

Matt: I am currently most excited about understanding how and why nature uses different transient interactions to control the fabrication and viscoelastic mechanical responses of biopolymeric materials and the potential this has for the development of sustainable advanced polymers of the future. Recent discoveries in the field clearly show that in contrast to traditional polymers, living organisms commonly use specific supramolecular interactions based on dynamic bonds (e.g. hydrogen bonding, metal coordination or pi-cation interactions) to guide the self-assembly and mechanical properties of protein-based materials. The thermodynamic and kinetic properties of these labile bonds enable a certain dynamicity and responsiveness in these building blocks that provides potential inspiration for environmentally friendly materials processing and active/tuneable material properties. These concepts are already being adapted in a number of exciting bio-inspired polymers.

 

What progress has the field made in the last years?

 

Kerstin: It is now well-established that cells are able to sense and respond to the elastic and viscoelastic properties of the material they grow in. We have also learned a lot about how the mechanical signal is converted into biochemical signalling on the intracellular side. This is a direct result of many new technological developments, including the molecular force sensors described above. It is further a result of the increasing development of extracellular matrix mimics with well-defined and tuneable mechanical properties and microstructures.

 

Matt: Due to recent technological advances it is becoming possible to link specific aspects of mechanical material responses directly to structural features at multiple length scales. The better we understand these structure-property relationships, the better we can optimize the material response. This provides an intimate feedback loop that has enabled major breakthroughs in the fields of active matter, including self-healing and self-reporting polymers.

 

What is the real-world impact?

 

Kerstin: It is widely accepted that mechanical information plays a key role in stem cell differentiation. It has further been shown that mutated cells, e.g. in cancer or cardiovascular diseases, have different mechanical properties and show alterations in processing mechanical information. Understanding the origin of these changes and being able to interfere with them will have direct impact in disease diagnostics and treatment. Engineering materials with molecularly controlled structures and mechanical properties will further enable the community to direct stem cell differentiation in a more defined manner for applications in tissue engineering and regenerative medicine.

 

Matt: Aside from biomedical impacts, the insights gained from understanding the structure-function relationships defining the mechanical response of molecules are also extremely relevant for the development and sustainable fabrication of next generation advanced polymers. Given the global threat of petroleum-based plastics processing and disposal, this is an extremely important aspect of the research in this field.

 

What are the challenges and future developments of the field?

 

Kerstin: At this moment, we usually try to relate the macroscopic material properties (measured in the lab) with the microscopic environment that cells sense. In my view, we are missing a key piece of information. We need to understand how the macroscopic properties of a material emerge from its molecular composition, topography and hierarchical structure. In combination, all these parameters determine the mechanical properties of a material and, more importantly, what the cells ‘see’. In fact, this is not only key for the development of new extracellular matrix mimics. The same questions need to be answered for understanding how nature assembles a wide range of structural and functional materials with outstanding properties, such as spider silk, cellulose composites and nacre. Here, I see a great potential for future collaboration between disciplines.

 

Matt: There are enormous challenges on the bio-inspiration side of the field involved with transferring design principles extracted from biological materials into synthetic systems. Biology is inherently complex, so there is a common tendency to distil the extracted concept to a single functional group or concept, while often there are collective effects that are lost by this more reductionist approach. On the biological side, a key challenge is ascertaining which are the relevant design principles. On the bio-inspired side, there are challenges in finding appropriate synthetic analogues to mimic the chemical and structural complexity of the natural system. Overcoming this barrier requires cross-disciplinary communication and feedback and is an extremely exciting and active area in our field.

 

Why and when did you decide to organize a conference on this topic?

 

Kerstin & Matt: While both working at the Max Planck Institute of Colloids and Interfaces, we quickly realized that the cell biophysics, biomaterials, mechanochemistry and soft matter communities are all interested in very similar questions while using similar methods and theoretical models; however, we had the impression that they hardly interact with each other. We thought of ways to change this and organizing a conference was clearly one way to do it. The first conference with the topic ‘Multiscale Mechanochemistry and Mechanobiology: from molecular mechanisms to smart materials’ took place in Berlin in 2017. When bringing this idea forward in our respective communities, we immediately realized that we hit a nerve. Now that the conference has taken place for the second time in Montreal in 2019, we really got the feeling that we are starting to create a community around this topic. There will be another follow up conference from August 23-25, 2021 in Berlin (@mcb2021Berlin).

 

What are the most interesting and representative papers published in PLOS ONE in this field?

 

Kerstin: The paper ‘Monodisperse measurement of the biotin-streptavidin interaction strength in a well-defined pulling geometry’, published by Sedlak et al., is a highly interesting contribution to the field of single-molecule force spectroscopy, which was also presented at the conference. This work highlights the methodological developments in single-molecule force spectroscopy since its very early days. The authors from the Gaub lab have re-measured the well-known streptavidin-biotin interaction, now with a very high level of control over the molecular setup. It clearly shows how far the field has come and also that protein engineering, bioconjugation chemistry, instrumentation development and data analysis all need to go hand in hand to obtain clear and unambiguous experimental results. Clearly, considering a defined molecular setup is not only crucial for this kind of measurement but also for the development of biomimetic materials with controlled mechanical properties.

 

Sedlak SM, Bauer MS, Kluger C, Schendel LC, Milles LF, Pippig DA, et al. (2017) Monodisperse measurement of the biotin-streptavidin interaction strength in a well-defined pulling geometry. PLoS ONE 12(12): e0188722, https://doi.org/10.1371/journal.pone.0188722 

 

Matt: Accurately detecting and measuring the mechanical forces at play inside living cells is one of the key challenges in the field of mechanobiology, given the small size and dynamic nature of the intracellular environment. However, this information is extremely important for understanding the role of mechanics in regulating cellular functions such as growth, differentiation and proliferation, as well as disease states. In the ‘Nuclei deformation reveals pressure distributions in 3D cell clusters’ paper from the Ehrlicher group, the authors address this challenge by using fluorescently labelled proteins in the cell nucleus coupled with confocal microscopy to measure compressive pressures within cells and cell clusters. Using this methodology, they explored the effect of cell number and shape of multicellular clusters on the internal compressive pressure within cells, providing potentially important insights for cellular signalling and function. These studies have potential applications in both in vitro and in vivo models, and provide a relatively simple methodology for acquiring intracellular mechanical data.

 

Khavari A, Ehrlicher AJ (2019) Nuclei deformation reveals pressure distributions in 3D cell clusters. PLoS ONE 14(9): e0221753, https://doi.org/10.1371/journal.pone.0221753

 

 Other PLOS ONE representative papers:

 

  • Huth S, Sindt S, Selhuber-Unkel C (2019) Automated analysis of soft hydrogel microindentation: Impact of various indentation parameters on the measurement of Young’s modulus. PLoS ONE 14(8): e0220281, https://doi.org/10.1371/journal.pone.0220281
  • Taufalele PV, VanderBurgh JA, Muñoz A, Zanotelli MR, Reinhart-King CA (2019) Fiber alignment drives changes in architectural and mechanical features in collagen matrices. PLoS ONE 14(5): e0216537. https://doi.org/10.1371/journal.pone.0216537
  • Wheelwright M, Win Z, Mikkila JL, Amen KY, Alford PW, Metzger JM (2018) Investigation of human iPSC-derived cardiac myocyte functional maturation by single cell traction force microscopy. PLoS ONE 13(4): e0194909. https://doi.org/10.1371/journal.pone.0194909
  • Opell BD, Clouse ME, Andrews SF (2018) Elastic modulus and toughness of orb spider glycoprotein glue. PLoS ONE 13(5): e0196972. https://doi.org/10.1371/journal.pone.0196972
  • Yalak G, Shiu J-Y, Schoen I, Mitsi M, Vogel V (2019) Phosphorylated fibronectin enhances cell attachment and upregulates mechanical cell functions. PLoS ONE 14(7): e0218893. https://doi.org/10.1371/journal.pone.0218893

 

Kerstin Blank studied Biotechnology at the University of Applied Sciences in Jena and obtained her PhD in Biophysics under the supervision of Prof Hermann Gaub at Ludwig-Maximilians Universität in Munich. After two postdocs at the Université de Strasbourg and the Katholieke Universiteit Leuven, she became an Assistant Professor at Radboud University in Nijmegen in 2009. In 2014, she moved to the Max Planck Institute of Colloids and Interfaces where she holds the position of a Max Planck Research Group Leader. Her research interests combine biochemistry and single molecule biophysics with the goal of developing molecular force sensors for biological and materials science applications.

 

Matthew J. Harrington is Canada Research Chair in Green Chemistry and assistant professor in Chemistry at McGill University since 2017. He received his PhD in the lab of J. Herbert Waite from the University of California, Santa Barbara. Afterwards, he was a Humboldt postdoctoral fellow and then research group leader at the Max Planck Institute of Colloids and Interfaces in the Department of Biomaterials. His research interests are focused on understanding biochemical structure-function relationships and fabrication processes of biopolymeric materials and translating extracted design principles for production of sustainable, advanced materials.

 

The post Physical forces at the interface with biology and chemistry: a conversation with Kerstin Blank and Matthew Harrington appeared first on EveryONE.

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.

 

The post It’s the little things- An interview with the Guest Editors of our Microbial Ecology of Changing Environments Call for Papers appeared first on EveryONE.

An Interview with Guest Editors for the Photovoltaic Materials Call for Papers

One of the most pressing challenges of the 21st century is meeting the ever-increasing demand for energy consumption whilst reducing the environmental impact of energy production and storage. Solar energy conversion devices have the potential

Tackling global biodiversity loss – An Interview with Biodiversity Conservation Call for Papers Guest Editor

  Human-induced environmental changes constitute the greatest current threat to biodiversity, comparable with other major extinction events observed in the Earth’s history. Biodiversity is the backbone of ecosystems and maintaining diversity through conservation is important