The Symposium

During the 3-day meeting, we will discuss microbial omics approaches associated with human, gut, and environment where computational advancements have been made to analyze biological "big data". Microbial omics and its translational aspects will be correlated with new biotechnological discovery. In addition, renowned scientists will be presenting how the microbial omics technologies are enabling for the safe exploration of future space missions with respect to astrobiology and planetary protection.

The study of microbial communities or microbiomes has widespread applications, from human health, agriculture and animal husbandry to waste treatment, bioremediation and environmental health. We foresee that a critical emerging technology is the ability to model and engineer microbiomes and leverage their extraordinarily diverse functional capacities to find solutions for many of the challenges that we face, from eliminating childhood malnutrition to degrading plastics, to exploring other planets.

Through this mini-symposium, we seek to bring leading scientists from India and abroad and to present their recent findings, and discuss important directions and ideas for fostering a strong microbiome community in India. There is also an opportunity for early career researchers to actively participate and contribute.

Organisers

Schedule

31 October 2022

Time Speaker Talk title
0900‑0930  Opening of the Symposium
Session 1: Space Microbiome (Session Chair: Kasthuri Venkateswaran)
0930-1000 Nick Benardini Unlocking the Spacecraft and Human Habitat Microbiome to Enable the Next Generation of Space Exploration
1000-1030 Nitin K Singh (Virtual) Plant Growth in Space and Microbiome
1030-1100 Coffee Break
1100-1130 David Reed Engineering perspectives on conducting spaceflight investigations utilizing plants, microbes, and other model organisms
1130-1200 Fathi Karouia Trends and Challenges Towards Biotechnology Applications in Space
1200-1300 Kasthuri Venkateswaran Keynote: Microbes in Space: Issues and Solutions about “Omics in Space”
1300-1430 Lunch
Session 2: Environmental Microbiome (Session Chair: Alexandre Rosado)
1430-1500 Fumito Maruyama (Virtual) Unique unseen neighbors in the Japanese built environments
1500-1530 Punyasloke Bhadury Exploring intricacy of coastal biogeochemical cycling: the importance of microbial biocomplexity
1530-1600 Silvano Onofri (Virtual) Searching for life from Antarctica to Mars
1600-1630 Alexandre Rosado Desert Microbiomes: Extreme Microbes from Antarctica and Saudi Arabia
1630-1700 Scott Tighe (Virtual) Genomics beyond the Twilight Zone: Strategies for Profiling the Dark Matter from Extreme Environments
1700-1800 Poster Session + Tea Break
1800-1930 Amazing Caves Video Screening
1930 onwards Dinner

1 November 2022

Time Speaker Talk title
Session 2: Environmental Microbiome
0900‑0930  Tamas Torok (Virtual) R&D with Chernobyl fungi
Session 3 Gut Microbiome (Session Chair: Stefan Green)
0930-1000 Stefan Green Effects of Spaceflight on the Mammalian Gut Microbiome
1000-1030 Coffee Break
1030-1100 Georgios Miliotis (virtual) Shotgun metagenomics analysis of the salivary microbiome reveals taxonomic and functional changes in young adults with depression
1100-1130 Marcus Teixeira Application metabarcoding analyses in burrow and cave ecosystems to track spillover events and the emergence and re-emergence of fungal pathogens
1130-1200 Yogesh Shouche (virtual) Human Microbiome in health and disease: Indian Perspective
1200-1230 Lightning Talks
1230-1330 Lunch
Session 4 Applications: Human Health & Biotechnology (Session Chair: Aloke Kumar)
1330-1400 Daniela Bezdan (Virtual) Novel biomedical applications and automated hardware for microgravity research and non-invasive astronaut health monitoring on the ISS and beyond
1400-1430 Aarthi Ravikrishnan (Virtual) Gut metagenomes of Asian octogenarians reveal a metabolic shift and distinct microbial species associated with aging phenotypes
1430-1500 Tulika Srivastava Associations of the Gut microbiota composition and functional dynamics with the host genes and dietary factors
1500-1530 Aloke Kumar Bio-cementation and extra-terrestrial habitats for humanity
1530-1600 Coffee Break
1600-1700 Poster Session

2 November 2022

Time Speaker Talk title
Session 5 Computational Approaches Session Chair: Narendra Dixit
0900‑0930  Narendra Dixit EPICS: An efficient top-down method for predicting structures of microbial communities
0930-1000 Karthik Raman Computational Approaches to Decoding Microbial Interactions in Microbiomes
1000-1030 Nikos Kyrpides Microbiome Data Science: from the Earth Microbiome to the Global Virome
1030-1100 Stephan Ossowski (Virtual) Ultra-deep sequencing of microbial and viral populations reveals intra-species genomic variations
1100-1130 Coffee Break
1130-1230 Panel Discussion: Path Forward for Indian Microbiome Research
1230-1300 Valedictory
1300-1400 Lunch
1430-1530 Visit to Research Park
1600 Depart for Airport

About IBSE

The Centre for Integrative Biology and Systems medicinE (IBSE), a CoE, at IIT Madras is an interdisciplinary centre dedicated to pioneering innovative approaches and algorithms that integrate multi-dimensional data across scales, to understand, predict and manipulate complex biological systems. The centre closely collaborates with Robert Bosch Centre for Data Science and Artificial Intelligence (RBCDSAI), one of the premier data science and AI centres in India.

The main sponsor, Indian Institute of Technology Madras, Chennai, is the top-ranked engineering institute in the country; and encourages interdisciplinary research at the interface of engineering, including computer science and biomedicine. While being situated in the heart of a busy metropolis, Chennai, the campus boasts hundreds of acres of forests, which are also home to various birds and animals, including the endangered blackbuck.

Funding

IBSE is grateful to Dr. Prakash Arunachalam, Lead Data Scientist, BNY Mellon, USA, for his generous contribution supporting the IBSE and funding the IBSE International Symposia and various other IBSE activities through the Office of Alumni and Corporate Relations, IIT Madras.

Acknowledgements

IBSE is grateful to Prof. Ashok Venkitaraman, Mehta Distinguished Chair, IIT Madras, and Director, Cancer Science Institute of Singapore, NUS Center for Cancer Research, Singapore, for his continued mentorship.

Abstracts

J. Nick Benardini

Unlocking the Spacecraft and Human Habitat Microbiome to Enable the Next Generation of Space Exploration

Planetary protection is the discipline that prevents harmful contamination of the solar system during exploration activities. The current international guidelines and NASA policy addressing biological contamination on spacecraft surfaces contains prescriptive guidelines of spore requirements (e.g., 300 spores/m2, 5×105 spores per spacecraft) applicable to spacecraft bound for Mars. To verify these requirements spacecraft engineers sample spacecraft surfaces throughout the assembly, test and launch operations phase of the mission using damp water cotton swabs and polyester wipes. After sampling, the potential biological contamination is enumerated using a series of traditional microbiology techniques to include sonication, heat shocking at 80°C for 15min to select for spores, and growth on tryptic soy agar at 32°C for 72 hours. To enable crewed missions to Mars and robotic exploration of the Ocean Worlds a risk informed decision making / performance-based approach to assess biological contamination offers a promising solution in the trade space. Recognizing the need for a performance-based approach, NASA’s new Planetary Protection policies now incorporate the agility for missions to be able to leverage a performance or prescriptive approach. One of top contenders in the option space is a coupled quantitative, descriptive and functional based approach to be able to assess the quantity, types and capabilities of the biological contamination present on spacecraft surfaces. A tailored, mission by mission assurance case could then be formulated by building an argument around the target body, projected capabilities surrounding the types of organisms their potential for survival and proliferation, and ability to be transported on the target body to contaminate an area of biological interest. A performance-based requirement would then be used to demonstrate the mission’s compliance in protecting the planetary environment safety objectives. This symposium talk will showcase the background and need case for NASA to develop such a capability as well as provide an update on the efforts underway in developing a transparent and responsible performance-based approach to biological contamination assessments on spacecraft surfaces.

Nitin Kumar Singh

Plant Growth in Space and Microbiome

Plants are an essential component of the life support system on Earth and will likely be crucial for Human Space Exploration to, e.g., the Moon and Mars. Indeed, NASA's interest in growing plants in the space environment has led to the development of plant growth facilities such as the VEGGIE and Advanced Plant Habitat, currently both operational on the ISS. Yet, although these systems are effective at growing plants to sizes where the astronauts can actually consume them, it remains unknown how the spaceflight affects the microbial communities around the plants’ root systems and in turn, how these changes may be impacting upon the plant itself. NASA-JPL is advancing efforts to study how plants and their rhizosphere microbial communities accommodate to the spaceflight environment and, at a practical level, determine how these interactions might be used to improve plant growth during long-term spaceflight missions.

David Reed

Engineering perspectives on conducting spaceflight investigations utilizing plants, microbes, and other model organisms

The human spaceflight realm poses unique challenges for engineers who develop facilities to conduct biological experiments and potential biology-based life support systems for off-Earth habitation. Fractional gravity strongly influences fluid and thermal management both for keeping organisms alive and for proper system function. Mass, volume, power, and data must be minimized through all mission phases. Current spaceflight experiments vary in complexity from simple Petri dishes to closed loop feedback-controlled chambers that regulate biologically relevant parameters such as photosynthetic illumination, diurnal cycle, temperature, humidity, moisture, atmospheric constituency, and even fractional gravity. Redwire has developed and deployed several commercial facilities on the International Space Station capable of studying fruit flies, round worms, mammalian cells, and plants. These experiments seek to understand both fundamental biological processes and extend human exploration of other planets and deep space.

Fathi Karouia

Trends and Challenges Towards Biotechnology Applications in Space

For over 20 years of full-time occupation onboard the International Space Station (ISS) many space life science breakthroughs have been achieved. These were based on technological advancements that enable culture of cells and tissues. Similarly, many model organisms, invertebrates and vertebrates, and plants have been used to better understand the effects of space environments on biological systems. Despite the continuing development of space hardware to accommodate the culture or growth of living systems onboard space habitats there are many limitations associated with crew time, mass, volume, chemicals being used, and storage. The traditional space biology paradigm that relies on post-flight data analysis is increasingly becoming a bottleneck to attract talented scientists and enable discoveries. Space biotechnology is a nascent field aimed at applying tools of modern biology to advance our goals in space exploration. These advances rely on our ability to exploit in situ high throughput techniques for amplification and sequencing DNA, and measuring levels of RNA transcripts, proteins, and metabolites in a cell. These techniques, collectively known as ""omics"" techniques have already revolutionized terrestrial biology. Several on-going efforts are aimed at developing instruments to carry out ""omics"" research in space, on board the International Space Station and small satellites. For space applications these instruments require substantial and creative reengineering that includes automation, miniaturization and ensuring that the device is resistant to conditions in space and works independently of the direction of the gravity vector. Different paths taken to meet these requirements for different ""omics"" instruments are the subjects of this review. The advantages and disadvantages of these instruments and technological solutions and their level of readiness for deployment in space are discussed. Considering that effects of space environments on terrestrial organisms appear to be global, it is argued that high throughput instruments are essential to advance (1) biomedical and physiological studies to control and reduce space-related stressors on living systems, (2) application of biology to life support and in situ resource utilization, (3) planetary protection, and (4) basic research about the limits on life in space.

Kasthuri Venkateswaran

Microbes in Space: Issues and Solutions about “Omics in Space”

Microbiome of environmental surfaces and atmosphere samples in the International Space Station (ISS) were characterized in order to examine the relationship to crew and hardware maintenance. The Microbial Tracking projects generated a microbial census of the ISS environments using advanced molecular microbial community analyses along with traditional culture-based methods. Since the “omics” methodologies generated an extensive microbial census, significant insights into spaceflight-induced changes in the populations of beneficial and/or potentially harmful microbes were gained. Lessons learned from ISS missions on the microbial prevalence using amplicon sequencing, metagenomes, and resistomes will be discussed. In addition, while characterizing ~3,000 bacterial and fungal strains several novel species were discovered and characterization of these novel species will be presented. The virulence characteristics of fungi as well as production of secondary metabolites that are of biotechnological importance are revealed. NASA has made great strides in the past 10 years to develop a suite of instruments for the International Space Station in order to perform molecular biology in space. However, a key piece of equipment that has been lacking is an instrument that can extract nucleic acids from an array of complex human and environmental samples. The Omics in Space team has developed the simulated microgravity tested instrument for automated nucleic acid system capable of automated, streamlined, nucleic acid extraction that is adapted for use under microgravity. The performance of the device at remote setting in Yellowstone National Park was comparable to that in a laboratory setting. Such a portable, field-deployable, nucleic extraction system will be valuable for environmental microbiology, as well as in health care diagnostics. The findings from the Environmental “Omics” project (basic science) should be exploited to enhance human health and well-being of the closed system. In other words, the microbial tracking research aims to ""translate"" findings in fundamental research into medical practice (pathogen detection) and meaningful health outcomes (countermeasure development). The “omics” data sets were placed in the NASA GeneLab bioinformatics environment—consisting of a database, computational tools, and improved methods— that would subsequently be made open to the scientific research community to encourage innovation.

Fumito Maruyama

Unique unseen neighbors in the Japanese built environments

There are various kinds of microbes in our surroundings, such as in the air and indoors as well as tap water. Though they are quite small in size (< 100 μm in most cases) invisible with our naked eyes, they constantly interact us in our daily lives, and sometimes have significant impacts on our health. We have interested in the indoor airborne microbes, its sources, dynamics, and biotic-, abiotic-interactions. We have investigated the microbial community structure of showerhead feed water and biofilm formed inside the showerheads, both of which are important source of bioaerosol in the built environment. We have found that the water is homogeneous in community across the whole Japan, whereas the community in biofilms differ among individual houses. We have also studied a traditional Japanese thatched-roof house that has been monitored for temperature and relative humidity (RH) since 2018. The result indicates the lowest RH affects microbial growth. One interesting microbiological feature of this house is high percentage of Archaea, especially in the earthen floor and well water. This means that the microbial community in traditional Japanese houses is different from that in modern houses. It is important to monitor environmental parameters, such as temperature, relative humidity (RH), particulate matter, the number of people, human behavior, air flow and air components like CO2 and Rn to elucidate the dynamics of indoor microbial concentration and microbial community. Therefore, an experimental living room has now been established in our university and the relationship among those environmental factors and indoor microbes is being continuously monitored. These investigation and findings indicate that more researches related to local and traditional house microbes of the built environment could be useful for further bioprospecting in addition to state-of-art microbiological safety technology and to build better human microbiome mutualistic relationship.

Punyasloke Bhadury

Exploring intricacy of coastal biogeochemical cycling: the importance of microbial biocomplexity

The coastal Bay of Bengal of the Northern Indian Ocean is home to a variety of biotopes with rich biodiversity, influences regional climatic patterns and supports the livelihood of millions of communities. Sundarbans, the world’s largest contiguous mangrove ecosystem, an UNESCO World Heritage Site and a RAMSAR site, located along the north east coast of the Bay of Bengal is home to unique biodiversity and abundant marine bioresources. However, there is a limited understanding of biocomplexity of microbiomes in mangroves that is shaped by prevailing environmental gradients which could have huge consequences on understanding many key ecosystems level processes including biogeochemical cycling of carbon and nitrogen. Understanding fluxes and rates of carbon cycling influenced by microbes or vice versa can have far reaching consequences towards improved estimation of regional carbon fluxes, in particular the budget of carbon in coastal oceans. Using a series of combinatorial approaches including through the establishment of a decade old time series- Sundarbans Biological Observatory Times (SBOTS) and high-throughput genomics using environmental DNA (eDNA), we are investigating how structure and function of microbiomes in mangroves including their functional complexities are shaped by forms of carbon and nitrogen. We have undertaken robust field mesocosm experiments to disentangle the functional significance of microbial complexity towards breakdown of complex forms of organic matter such as mangrove litterfall in Sundarbans. We have also initiated environmental surveillance of freshwater to coastal connectivity to get a better understanding of prevalence of antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) and possible implications in terms of changes in functional attributes of microbiomes for Sundarbans and across South Asia. Our ongoing studies show that unique forms of microbial communities in the waterscapes of Sundarbans have adapted to prevailing environmental gradients and are key players in processes such as biogeochemical cycling with far reaching consequences on a sustainable blue economy for South Asia.

Silvano Onofri

Searching for life from Antarctica to Mars

The McMurdo Dry Valleys in Antarctica are the coldest hyper-arid desert on Earth, characterized by several environmental stressors including low temperatures, freeze-thaw cycles, low water availability, high solar and UV irradiation. Imre Friedmann discovered life in Antarctic rocks and proposed cryptoendolithic communities as models for the search for life on Mars. Over the past 20 years we have studied the mycological component of Antarctic rocks, discovering dozens of new species. Some of these have been analyzed for their resistance to radiative stress, water, temperature, etc. In particular, Cryomyces antarcticus demonstrated to resist temperature cycles (- 20°C/+20°C), high temperature (+90°C), high saline concentration (up to 25% NaCl), high UV exposure (up to 5x105 kJ/m 2 ), ionizing radiation (Co 60 , up to 55.81 kGy) and heavy ions (He, Ar and Fe, up to 1000 Gy). Furthermore, it proved ability to survive to space conditions and Martian environment simulated in space when exposed for 18 and then 16 months on the outside of the International Space Station. Infact, during the ESA EXPOSE-E-LIFE experiment (Lichens and Fungi Experiment), C. antarcticus survived the vacuum and radiation in space as well as the radiation and atmosphere of Mars simulated in space; moreover, in the ESA-BIOMEX experiment, which one of the main objectives was to test the survival of selected extreme-tolerant/extremophilic microorganisms in extra-terrestrial conditions, C. antarcticus, cultivated both on recent and early Martian soil analogs, survived space and Martian conditions. Besides, in recent on ground based experiments in the Martian simulation chamber, C. antarcticus has shown the ability to metabolize under simulated Martian conditions. Considering the recent knowledge acquired on the possible existence of water on Mars, it can currently be hypothesized that fungal microorganisms, like those collected from Antarctica, may have been components of a putative past life on Mars.

Alexandre Rosado

Desert Microbiomes: Extreme Microbes from Antarctica and Saudi Arabia

The "extremobiosphere" are areas of the globe where harsh factors have pushed life to its limits. Therefore, microorganisms able to survive in such hostile environments may develop new chemical structures that could have important biotechnological applications. Cold or hot deserts and volcanic environments are part of the essence of Saudi Arabia and Antarctica. The extreme conditions in the terrestrial environments of Saudi Arabia make it one of the most inhospitable and interesting places on Earth for research on extremophiles. In this context, we targeted major extreme biomes in SA and Antarctica (Deception volcanic Island) to explore the microbial community diversity and their roles in these environments. Here we report the utilization of a multi-omics and cultivation-based framework to describe diversity and function as well biotechnological potential of non-culturable as well as novel bacterial isolates from these two very different extreme sites. Shotgun metagenomics showed the abundance of Cytophaga, Methyloversatilis, Polaromonas and Williamsia in hydrocarbon contaminated soil of Antarctica. The most abundant hydrocarbon degradation pathway was related to the degradation of the alkyl-PAH derivative (mainly methylnaphthalenes) via the CYP450 enzyme family. Al Wahbah Crater is one of the volcanic sites in Saudi Arabia with highly saline soils (Sodium- 23-59 g/kg). Culturomics showed the dominance of Firmicutes. In addition, many secondary metabolites with antimicrobial and antifungal properties were predicted. Sand samples from the AlUla desert were submited to UV-C irradiation (2000 J·m−2·s−1). We isolated UV-C resistant strains producing novel pigments. Altogether, our data provide insights into the metabolic potential of microbes from Saudi Arabia and Antarctica's extreme terrestrial environments with great potential for astrobiology and biotechnology.

Scott Tighe

Genomics beyond the Twilight Zone: Strategies for Profiling the Dark Matter from Extreme Environments

The ability to perform advanced genomic techniques on samples collected from extreme and novel environments demands a well designed experimental approach using high performance reagents and techniques not commonly using in most labs today. Our research in the Extreme Microbiobome Project uses the most advanced metagenomics protocols in including microscopy, culturing, novel DNA and RNA extraction, and sequencing using Illumina and Nanopore next generation sequencing technologies. DNA-free reagents, high performance lysis enzymes, multistep controls, high volume concentration, and sample pre-amplification can be used low biomass samples. Our research has performed microbiome and metagenomics analysis on extremophilic sites around the world and beyond including Greenland, Antarctica, Romanian caves, thermophilic ecosystems, halophilic, acidic, and alkaline lakes, as well as organisms from space. This presentation will discuss results from these extreme environments and the appropriate techniques to generate quality data.

Tamas Torok

Chernobyl fungi visit the ISS

Filamentous fungi are widely spread in the environment. They are particularly important as the ultimate decomposers of organic matter. Over the past few decades, increasing interest was generated by fungal strains that were reported to survive or proliferate under extreme environmental conditions. Among the many physical and chemical extremes ionizing radiation is probably the most fascinating one. For the origin of ionizing radiation resistance in biological organisms cannot be explained as an adaptation to environmental radiation. Natural sources of ionizing radiation on Earth emit at very low levels only compared to the acute doses to which some microorganisms show resistance. The 1986 accident at the Chernobyl nuclear power plant (ChNPP) and the enduring radiation have provided a scientific opportunity unlike any other to study filamentous fungi collected at the site. More than 2,000 fungal strains representing some 200 species and 98 genera were collected at and around the failed 4th reactor block of the Chernobyl nuclear power plant and the 10-km (later expanded to 30-km) exclusion zone over a period of 16 years. The resulting global picture showed relatively low complexity fungal communities. Sampling the sites over time and at varying distance from ChNPP often resulted in strains of fungal response to radiation. For example, some 80% of the highly melanized fungal strains detected closest to the failed reactor showed a phenomenon known as positive radiotropism, while none of the pristine environmental isolates behaved similarly. In cooperation with DuPont and Hi-Bred International, large-scale screening of the Chernobyl fungal strains for antifungal peptides and insecticidal molecules were performed. Laboratory test results were translated into successful transgenic crop plants to protect them from fungal pathogens and insect pests. Selected Chernobyl fungal isolates, carefully chosen following an exposure to simulated Martian UV-C conditions, made the voyage to the International Space Station (ISS) to be exposed to microgravity. The follow-up investigations have resulted in numerous publications dealing with adaptation changes, the potential role of pigmentation, specifically that of melanin, and the expression of biologically active secondary metabolites. The presentation will focus on the history of Chernobyl fungi and summarize some valuable findings.

Stefan Green

Effects of Spaceflight on the Mammalian Gut Microbiome

The microorganisms inhabiting the gastrointestinal tract interact with their mammalian host’s immune, metabolic, and psychological functions and play an important role in health. Stress factors associated with spaceflight, such as disturbances to circadian timing and sleep, confinement, lack of fresh produce or air, and extremely limited contact with others, may jeopardize a healthy, diverse gut microbiome, and risk astronaut health as well. To understand how the gut microbiome is changed by spaceflight, we have analyzed fecal microbiome composition in flight and ground subjects and compared the patterns of change detected from multiple rodent missions, and in human twins. We obtained fecal samples from mice aboard the International Space Station in the Rodent Research 1 Mission, and we profiled fecal microbial community using high-throughput amplicon sequencing of the microbial 16S rRNA gene. We found that the community structure of gut microbiota in spaceflight animals was significantly different from that observed in baseline, ground, and vivarium control groups. There was no decrease in diversity despite the stay in the confined space environment. We observed an increase in the relative abundance of Firmicutes and a decrease in the relative abundance of Bacteroidetes during flight in RR1 animals. We observed a similar increase in the ratio of Firmicutes-to-Bacteroidetes, and no loss in diversity in spaceflight, in the NASA Twins study. We developed an analytical tool, named STARMAPs to test for similarity of changes in different data sets. We compared the changes in RR-1 samples with published findings from a shuttle flight. Consistent changes associated with spaceflight were detected in the RR-1 and the shuttle data sets. STARMAPs was further used to test whether experiments introducing individual spaceflight-associated stresses could produce accordant microbiome changes. While many factors did not, sleep restriction did produce a similar change. We thus hypothesize that an altered microbiome may be a crucial link between sleep disruptions and other physiological changes observed during spaceflight. Our team is currently analyzing gut microbiota and multi-system physiology, including sleep and circadian rhythms monitored by video recordings, in data from Rodent Research 7, allowing us to directly test this hypothesis.

Georgios Miliotis

Shotgun metagenomics analysis of the salivary microbiome reveals taxonomic and functional changes in young adults with depression.

The oral microbiome comprises a community of over 1,000 bacterial species that reside in the oral cavity in several niches. Associations between oral dysbiosis and systemic diseases is well established, particularly with diseases that possess an underlying inflammatory component. Psychiatric disorders such as depression (major and minor) are amongst the leading causes of economic burden and disability worldwide. Despite depression’s prevalence, its underlying aetiology is poorly understood, though inflammation appears to be a key component. Recently, using 16Sr RNA metataxonomics analysis we indicated compositional differences between the oral microbiomes of healthy individuals and individuals with depression. To further characterise these differences, we employed shotgun metagenomics sequencing with the aim to characterise the composition and functional differences in the oral microbiome of individuals with depression compared to healthy controls. Deep shotgun metagenomics sequencing (>100million PE150 per sample) was conducted on the extracted DNA of the collected salivary samples for the two cohorts. Human reads were removed using Kraken 2 (v2.1.2). The taxonomic profiling for the depression associated and healthy cohorts was obtained using the co-assembly method of the SqueezeMeta pipeline (v.1.1.2). Open reading frame (ORF) prediction and annotation were retrieved by homology searching on co-assembly contigs using the COG and KEGG reference databases. Our analysis identified depression to be associated with a significantly decreased alpha diversity (p=0.047). One phylum, four genera and seven bacterial species were also differentially abundant between the two cohorts. In particular, we noted depression to be associated with a reduced abundance (p=0.031) of GABA producing species as well as we identified two species being almost exclusively in the depression associated cohort. Functional differential abundance analysis revealed the depression associated microbiome to have a lower abundance in KEGG orthologies (KOs) related to eleven molecular functions, including pathways linked with xenobiotic biodegradation and quorum sensing. Overall, characteristic differences in the composition and function of the oral microbiome have been identified in young adults with depression and our results suggest the presence of a dysbiotic oral microbiome in this cohort. The clinical importance of these results and their link with pathogenesis of depression require further studies and a multi-omics approach.

Marcus Teixeira

Application metabarcoding analyses in burrow and cave ecosystems to track spillover events and the emergence and re-emergence of fungal pathogens

Fungal infections contribute significantly to global human morbidity, affecting millions of people worldwide and killing more than 1.7 million people annually, surpassing deaths from tuberculosis and malaria or breast cancer. One-third of the human population has already acquired a fungal life during its lifetime. Despite this impact, mycoses are globally neglected with an urgently unmet need for prevention, effective treatment and accurate diagnoses. Pathogenic fungi are polyphylically distributed across the Fungi Kingdom with distinct evolutionary histories and adaptive strategies that have led to the emergence of diverse mechanisms of virulence and adaptation to living hosts. At least 300 pathogenic fungal species are likely to occur and many emerging pathogens in wildlife have not yet been described. Zoonotic spillover is characterized by the transmission of pathogens from wild animals to humans and has gained significant attention due to the SARS- CoV-2 pandemic. The emergence of zoonotic diseases occurs at different evolutionary stages on the pathogen side, following successive spillover events that propagate through human outbreaks, increasing the pathogen's adaptation for community transmission. Understanding the diversity of pathogens associated with environmental factors (drivers) that pave the way for the transmission of pathogenic species from wild animals to humans is crucial to developing control strategies to reduce the frequency of host-jumping events. Therefore, a multidisciplinary approach is needed, linking host and pathogen genetics, ecology, genomic epidemiology, traditional epidemiology, clinical and veterinary research, treatment and disease management in each respective field. Thus, metagenomics and qPCR-based approaches are considered fundamental in the monitoring of fungal infections. From the characterization of microorganisms present in animals such as bats, prairie dogs and armadillos, which are reservoirs for fungal species, it is possible to extrapolate that these microorganisms are potential sources of future emerging diseases. In this sense, we used qPCR and ITS-based sequencing coupled with phylogenetic inferences to identify pathogenic fungi associated with those mammals. We have identified known and unknown fungal pathogens related to those ecosystems such as Histoplasma sp., Coccidioides sp. Blastomyces sp. Cryptococcus gattii and Pneumocystis sp. and novel species such as Emmonsieliopsis cynomosii or Blastomyces cynomosii that have pathogenic potential to humans. We have also quantified various ecological metrics such as alpha and beta diversity to quantify those pathogens between tissues and their habitats. We inferred that fossorial and troglobite mammals are important reservoirs for maintaining pathogenic fungi in the environment.

Yogesh Shouche

Human Microbiome in health and disease: Indian Perspective

The human gut microbiota is "the ecological community of commensal, symbiotic and pathogenic microorganisms that literally share our gastrointestinal tract". Dominated by eubacteria, the metabolic activities performed by the gut microbiome is often as complex as an organ and hence it is now being appreciated and studied in much detail. Increasing evidence suggests that the human gut microbiota changes according to diet, age, lifestyle, climate and geography, genetic make-up, early microbial exposure and health status. Studying the Indian population is relevant given the known dietary and geographical variety, unique family structure and ethnic diversity. In traditional Indian family system, where three generations can be studied for changes in the gut microflora with age, it has been shown that the gut microbiota changes according to age within individuals of the same family and a shift in the Firmicutes/Bacteroidetes ratio with age is observed, which is different than previously reported in European population. With the incoming wave of lifestyle changes observed now in India and given the availability of sugar-rich diet, the population is at high risk of developing obesity and diabetes. In the case of Diabetes, a consolidated dysbiosis of not just eubacterial but also of archaeal and eukaryotic components is seen in the gut microbiota of newly-diagnosed and known-diagnosed diabetic individuals as compared to healthy individuals. Comparative analysis of gut microbiota of healthy Indian subjects with other populations highlights that the gut microbiomes of Indians is different from that of other Western populations and even cluster separately from Asian populations. The distinctive feature of the healthy Indian gut microbiome is the predominance of genus Prevotella and Megasphaera. Taken together, the relevance of studying the Indian microbiome is justified given its unique microbiome features and further studies are necessitated to understand the determinants shaping the Indian microbiome. This will be helpful to develop microbial consortia for prebiotic and probiotic application and devise population specific microbiome therapies.

Daniela Bezdan

Novel biomedical applications and automated hardware for microgravity research and non-invasive astronaut health monitoring on the ISS and beyond

In recent years, an increasing number of government and private space agencies have formed to leverage low-orbit conditions for microgravity research, biotech production, and preparation for long-distance space exploration. As astronaut time is limited and costly and more and more missions will be uncrewed in the future, the requirement for automated and sustainable systems has increased dramatically. yuri is a space company located in Germany, Luxembourg, and the US, offering solutions for life science experiments and applications in a microgravity environment. Our hardware portfolio facilitates full automation and monitoring of biomedical experiments in modular and reusable ScienceShells. ScienceShells are customizable to utilize cell cultures and iPSC, lab-on-a-chip, or organoid-on-a-chip methods for and are extendable with various analytical tools such as microscopes (resolution 1µm, >25mm² field of view, bright- field & phase contrast, 3D-imaging), fluorescence imaging, backscattering, various sensors (e.g., O 2 /pH), and a camera, among other customizable tools. Combined with yuri’s novel mid-deck-locker size incubator ScienceTaxi featuring full automation, precise experiment control, and real-time data monitoring during the complete mission, this technology permits to start experiments immediately after reaching microgravity. The ScienceTaxi incubator has a temperature range of +4°C to +40°C and contains a centrifuge for simulating Earth, Moon, and Mars gravity in space. Such fully automated systems will be essential for uncrewed missions or considerably reduce the time and cost of monitoring astronaut health. Previously we described non-invasive astronaut health monitoring using liquid biopsy in collaboration with Weill Cornell Medicine, USA. To date, we are developing a novel technology for astronaut health monitoring, together with the University of Tübingen, which is even more accessible and easier to implement. In this non- invasive method, we use hair roots of plucked hair to isolate cells as source material for health monitoring, Next Generation Sequencing, and generation of organoids, which also facilitates applications such as drug screening and biotechnological production. Biomedical research and bio-production in microgravity will help understand the inner workings of biological systems better and enable advancements in pharmaceutical development, tissue engineering, biotechnological manufacturing, agriculture, and material sciences in space. Here we present innovative biomedical applications for microgravity research on the ground, in lower orbit, and on the ISS and are excited to showcase our own biological experiments on the ISS in 2022 and our upcoming maiden flight of ScienceTaxi on the Dream Chaser in 2023.

Aarthi Ravikrishnan

Gut metagenomes of Asian octogenarians reveal a metabolic shift and distinct microbial species associated with aging phenotypes

While rapid demographic changes in Asia are driving the incidence of chronic diseases related to aging, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging the availability of a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun metagenomic sequencing to do high-resolution taxonomic and functional characterization of their gut microbiomes (n=234). Species-level analysis identified a distinct age-associated shift in Asian gut metagenomes, characterized by a reduction in microbial richness, and enrichment of specific Alistipes species (e.g. Alistipes putredinis, Alistipes onderdonkii). Functional pathway analysis confirmed that these changes correspond to a metabolic switch in aging from microbial guilds that typically produce butyrate in the gut (e.g. Faecalibacterium prausnitzii, Roseburia inulinivorans) to alternate pathways that utilize amino-acid precursors. Extending these observations to key clinical markers helped identify >15 robust gut microbial associations to cardiometabolic health, inflammation, and frailty, including potential probiotics such as Parabacteroides goldsteinii and pathogenic species such as Dialister invisus, highlighting the role of the microbiome as biomarkers and potential intervention targets for promoting healthy aging.

Tulika Srivastava

Associations of the Gut microbiota composition and functional dynamics with the host genes and dietary factors

Human gut is colonised by 1011 bacteria per gram which perform a variety of roles related to host health and maintaining the gut-microbiota homeostasis is crucial for health of the host. A number of factors can influence the gut- microbiota structure and species abundance directly or indirectly, including host genes and diet. The dysbiosis of the gut-microbiota has been linked to a variety of diseases, and managing its structure and diversity is an important part of controlling disease progression. Prebiotics, probiotics, and FMT can all be used to manipulate the gut-microbiota, which all appear to be appealing alternatives for illness prevention and treatment. All these strategies are possible only if the roles of the different microbial members are clearly understood. The recent advancements in the sophisticated research methodologies have immensely helped to clarify the roles of some of the microbial members of the gut. However, the potential roles of several other members of the gut microbiome still remains unknown. The broad scope of this work is to explore the roles of the members of the gut microbiome in intestinal immunity. Based on the available research some host intrinsic and extrinsic factors are broadly known to impact the gut microbiota. The major host intrinsic factors include the host genetics and the biogeography of the microbiota in the gut. The most important extrinsic factor which is known to influence the gut microbiota is host diet. Although a large number of studies have explored the impact of several host immune molecules on gut microbiota dynamics, the microbial association of many other immune associated processes have still remained unexplored. Since one of the prominent roles of the gut microbiome is to maintain the intestinal immune homeostasis, the host genetic factors associated with the immune system are expected to have profound influence on the gut microbiota. With respect to the gut associated immunity, the polarity of the intestinal epithelial layer plays a very important role in microbial surveillance and defense. In the present work, we have explored the association of two such important immune related molecules, namely epithelial specific adaptor protein AP-1B and GPI- anchor biosynthesis related Piga gene which are known to be involved in maintaining the polarity of the intestinal epithelial cells (IECs). Using the next- generation sequencing based whole metagenome shotgun sequencing approach, we examined the fecal microbiota composition in Ap1m2+/- and Ap1m2-/- mice and highlighted the role of the gut microbiome in the colitis phenotype induced due to this gene knockout. Similarly, the intestinal epithelium specific Piga gene knockout was created in mice and its subsequent impact on the fecal microbiome composition and function was explored. Diet is necessary for development, health, and reproduction and plays a major role in modulating the gut microbiota. The dietary fibers interact directly with the gut microbes and lead to the production of key metabolites such as short-chain fatty acids (SCFAs). The soluble and insoluble fibers are known to be metabolised differently by the gut microbiota. Also, the amount of fibre administered has shown to be associated with different phenotypes with respect to gut health. In this work, we have explored the associations of two major dietary fibers on host health. We explored the effect of prebiotic Fructooligosaccharides (FOS) administration on gut microbiome by performing comparative microbiota analysis of mice fed with FOS over a period of 7 days. Further, we explored the effect of grain-based (GB) diet containing both soluble and insoluble fibers and purified ingredients-based (PIB) diet containing only insoluble fiber, namely cellulose, on gut microbiota by feeding mice with these diets for 2 months. In summary, in this work whole metagenome shotgun sequencing is extensively used to explore the understudied factors associated with the gut microbiota variance. The results are of interest in progressing the understanding of influencers of microbiota composition and microbial interactions with host health.

Aloke Kumar

Bio-cementation and extra-terrestrial habitats for humanity

Biomineralization refers to the process of mineral precipitation due to chemical alteration of the environment induced by the microbial activity. For unicellular organisms such as bacteria, the biomineralization process can be either extracellular or intracellular. Microbial induced calcite precipitation (MICP) is an excellent example of an extracellular mineral deposition. Several microbial species take part in biocementation through MICP by means of various mechanisms such as photosynthesis, urea hydrolysis, sulfate reduction, anaerobic sulfide oxidation, biofilm and extracellular polymeric substances. In this talk, I will present our investigations on the fundamental understanding of the MICP process at the cellular level as well as its applications. I will present our findings on how MICP can be employed for both hardening of extra-terrestrial regoliths into ‘space bricks’.

Narendra M Dixit

EPICS: An efficient top-down method for predicting structures of microbial communities

Predicting structures of microbial communities requires knowledge of the inter-species interactions involved. With high-order interactions, the number of such interactions scales exponentially with the number of species. Bottom-up approaches, which consider all individual, two species, three species, etc. subcommunities, to unravel the interactions thus require a prohibitively large number of experiments. Here, we propose an alternative, top-down approach. We show how using leave-one-out sub-communities, which comprise all subcommunities formed by leaving one species out at a time, along with individual species cultures enable estimation of effective pairwise interactions that subsume high-order interactions. With these effective pairwise interactions, we can predict the structures of communities accurately. We show its applicability to a synthetic community representative of the human oral microbiome. This algorithm, termed EPICS, is efficient and scalable, and brings us closer to predicting structures of natural microbiomes.

Karthik Raman

Computational Approaches to Decoding Microbial Interactions in Microbiomes

Metabolic interactions are known to drive the organisation of various microbiomes. It is of great interest to study the possible interactions between microbes in communities, understand the keystone species in these microbiomes, and how they influence one another and ultimately shape the structure of the microbiome. In this talk, I will focus on computational approaches we have developed, to understand the organisation of a variety of microbiomes, focussing on their metabolic networks. We have used complementary approaches from graph theory and constraint-based modelling to systematically study microbiomes ranging from those in the human gut and the eye, to extreme environments such as those aboard the International Space Station and deep-sea hydrothermal vents. In each of these environments, we identify unique interaction patterns and possible metabolic exchanges and dependencies amongst the organisms. We have developed a suite of novel computational approaches to study these microbial communities and understand key organisms and dependencies underlying these complex systems. Metabolic modelling, through a combination of graph-theoretic approaches and steady-state constraint-based modelling, paints a more comprehensive picture of possible microbial interactions, which are as yet inscrutable to this extent by experimental approaches. Our results point toward key dependencies of microorganisms in various environments. Our approach also underscores the importance of complementary modelling approaches in dissecting a fairly complex microbiome and understanding various possible interactions. Our methodology is fairly generic and can be readily extended to predict microbial interactions in other interesting milieu and generate testable hypotheses for wet lab experiments.

Nikos Kyrpides

Microbiome Data Science: from the Earth Microbiome to the Global Virome

Microbiome research is rapidly transitioning into Data Science. The unprecedented volume of microbiome data being generated pose significant challenges with respect to standards and management strategies, but also bear great new opportunities that can fuel discovery. Computational analysis of microbiome samples involving previously uncultured organisms, is currently advancing our understanding of the structure and function of entire microbial communities and expanding our knowledge of genetic and functional diversity of individual micro-organisms. I will describe some of our computational approaches and will emphasize the value of data processing integration in enabling the exploration of large metagenomic datasets and the discovery of novelty. I will present current approaches and will discuss a few science vignettes in the exploration of microbial, viral, and functional diversity.

Stephan Ossowski

Ultra-deep sequencing of microbial and viral populations reveals intra-species genomic variations

Viruses mutate rapidly and hundreds of mutations have been detected in the SARS- CoV-2 genome, some of which can increase infection rates as reported for the Omicron BA.5 variant. Novel mutations can also affect the accuracy of diagnostic tests, the efficiency of vaccines, and may associate with clinically relevant phenotypes (disease severity, response to treatment). Viral whole genome sequencing can readily reveal novel mutations and thereby contribute to an improved understanding of virulence and the reconstruction of worldwide transmission routes. A focus of our study is the characterization of intra-host viral diversity and evolution, and the detection of low-frequency viruses in a host’s SARS- CoV-2 population. We demonstrate that our approach combining ultra-deep sequencing, unique molecular barcodes and a newly developed SNV detection method outperforms other approaches and can detect mutations with an intra-host- frequency below 0.1%. In a second project we used ultra-deep Nanopore sequencing to de novo assemble genomes of microbiomes collected from soil samples, with the goal to identify novel species, genes, biosynthetic gene clusters and specialized microbial metabolites in metagenomes.

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Indian Institute of Technology Madras
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