The Centre for BioSystems Science and Engineering (BSSE) at the Indian Institute of Science (IISc), Bangalore, India has brought together biologists, engineering, and those who are trained as bioengineers while also extending its reach to medical doctors, agricultural scientists, and biomedical industries to train the next generation of leaders in the field. BSSE currently hosts three permanent faculty, twelve associate faculty, one INSPIRE fellow and forty-two PhD students. Our faculty have expertise in a range of disciplines and conduct groundbreaking research providing students with a myriad of opportunities.
The BSSE Research Symposium is an annual event with a goal to increase collaboration and allow the exchange of new ideas between students, researchers, industry partners and clinical practitioners. The 7th BSSE Annual Research Symposium will be a two-day virtual event on the 19th and 20th of February, 2021. The two-day symposium will aim to have engaging scientific discussions with themed sessions like biomaterial-cellular interfaces, systems biology, tissue engineering, biomedical systems among others to highlight the multifaceted nature of interdisciplinary research performed in BSSE in an intuitive and interactive virtual environment. We will end the symposium with an exciting and unique panel discussion on "Shifting goalposts: Research in a post-COVID-19 world". We anticipate an excellent and diverse program of events and opportunities to connect with fellow peers and continuing the legacy of BSSE symposia, even while in an online format. Please share this announcement with colleagues and students who may be interested.
To encourage scientific commincation, we are organizing an online competition that requires participants to record a video (3-5 min) of themselves talking about their research/project work in a way that is understandable and thought-provoking to a non-technical general audience. This video then needs to be uploaded on YouTube as a private unlisted video and shared with us. Further details are in the registration form.
We look forward to meeting you all!
|Introduction and Inauguration||10:30-10:55||Inaugural function: Addressed by Dean of Interdisciplinary Sciences and BSSE chair|
|Sanjay Kumar Biswas Memorial Lecture||10:55-12:00||Prof. Manu Prakash
Title: Extreme biophysics: Learning from limits of living systems
|Session 1: Biomaterial-Cellular Interfaces||12:00-12:40||Prof. Nitin Baliga
Title: Spatiotemporal heterogeneity, personalized medicine and AMR
Complex properties such as robustness and resilience of biological systems emerge from spatiotemporal heterogeneity. Cancerous cells and pathogens exploit spatiotemporal heterogeneity to evade the immune system and drugs. I will discuss how causal and mechanistic understanding of gene networks that generate spatiotemporal heterogeneity from bulk populations to single cells will be central in our fight against cancers and recalcitrant infections.
|12:55-13:20||Student Talk: Kaamini M. D.
Title: Rapamycin carriers for treatment of Osteoarthritis
Osteoarthritis (OA) having affected nearly 22-39% of the Indian population, remains as one of the most common musculoskeletal disorder that affects articular joints. It results in disability with severe impact on the associated morbid life increasing the society’s burden. The current standard of care mainly attributed to the lack of disease-modifying drugs in the clinics, revolves around symptomatic treatment and total knee arthroplasty. Even though research on OA treatments is brimming, numerous disease-modifying drugs are bottlenecked at the translational phase. This is due to their poor bioavailability at the affected site, necessitating multiple injections, and decreased patient compliance. Thus, the need of the hour is a simple delivery carrier that is easily translatable, successful in clinics with the added benefit of ease in tuneability of drug release. Rapamycin, a widely used immunosuppressant, has proven abilities to prevent senescence in chondrocytes and could potentially prevent the progression of OA disease in murine models. But clinical translation of these drugs for OA treatment have been slow due to frequent dose regimens involving multiple injections weekly which reduces patient compliance. Herein our project, we have fabricated PLGA microparticles (MPs) containing rapamycin and optimised their release profiles to extend the drug release up to 120 days. These were tested in vitro for their potency on human articular chondrocytes (C28/I2). The MPs were able to induce autophagy in a dose- dependent manner very similar to free drug, prevented senescence in cells subjected to various stresses and sustained sGAG production up to 8 days. When surgically OA induced mice models were treated with rapamycin MPs with a prophylactic regimen, the RMPs were able to prevent the onset of OA disease compared to the untreated controls or free drug treated group. On the same lines when surgically OA induced mice were treated with RMPs as a therapeutic regimen, with treatments starting after 3 weeks of surgery, they were able to prevent the progression of OA compared to untreated controls. Thus, this particulate formulation has shown to be a promising candidate for using rapamycin in prospective osteoarthritis treatment in clinics.
|13:25-13:50||Student Talk: Alakesh Singh
Title: Sterile inflammation alters neutrophil kinetics in mice
Implantation of sterile biomaterials elicits an immune response that involves a number of innate immune cells. Of these cells, neutrophils are the first responders, and their increased presence is suggested to result in damaging inflammatory reactions. Modulating neutrophil numbers and function could aid in reducing inflammation and improving biomaterial compatibility, however, in the context of implantations the rate of recruitment, residence time, and activity of neutrophils remains poorly characterized. Therefore, at first, we want to know the residence time of neutrophils at the implant site as this information will dictate the rate of recruitment and overall functionality of the neutrophils. To answer this question, with the help of mouse models, we propose to experimentally determine the residence time of neutrophils and use mathematical models to estimate the half-life of these cells at implant sites.
|Lunch Break||13:55-14:45||Lunch Break|
|Session 2: Tissue Engineering||14:50-15:30||Prof. Rebecca Shipley
Title: Integrating in-silico, in-vitro and in-vivo models in peripheral nerve tissue engineering
|15:35-16:10||Prof. Jyotsnendu Giri
Title: Nano-micro system to overcome protein delivery challenges for biomedical application
Protein depot formulations (Microparticulate or scaffold) for long-term controlled release of active therapeutic protein have immense clinical importance for the treatment of many diseases, conditions, and regeneration of specific tissues. Despite the high potential of biodegradable polymer-based such depot, clinical success has been limited for few small molecules and peptide/protein formulation, mainly due to the presence of critical barriers such as low encapsulation efficiency, uncontrolled release, and activity losses during processing and storage. We have developed novel proteins-nanoencapsulation system namely, sugar-glassnanoparticles (SGnP) and sugar-Silk Fibroin-nanoparticles (sSFnP) to overcome the challenges. We are using these novel nanoencapsulation systems as a generic platform to develop sustain release “protein depot” and ‘smart biomaterials’ for therapeutic protein delivery and potential functional tissue regeneration respectively.
|16:15-17:00||SciComm Videos Screening|
|17:05-17:30||Student Talk: Parul Yadav
Title: Understanding cellular senescence in three-dimensions
Aging is an unavoidable and temporal decline of physiological functions of an organism. This progressive deterioration starts early on at cellular level (senescence) and overtime leads to development of age-related disorders such as atherosclerosis, heart failure and osteoporosis etc. As aging is the root cause of several degenerative diseases, understanding it at cellular level, i.e., cellular senescence is of utmost importance. Cellular senescence is essentially described as a process in which cells cease to divide and undergo distinctive phenotypic alterations. Conventionally, senescence studies are performed on two dimensional (2D) dishes where the cells become flat, lose their in vivo morphology, cell-cell and cell-matrix interactions, and thus 2D culture does not mimic the three dimensional (3D) complex cellular microenvironment in the human body. Given the limitations of 2D culture system, the cost and time required for animal studies, we aim to mimic the body's native environment in 3D polymeric scaffolds, thereby offering better insights into the molecular mechanisms of aging. In this work we designed and developed 3D polymeric scaffolds for senescent cells that would retain their in vivo phenotype, thus giving us a 3D cellular senescence model. This study will have potential applications to study the effect of senolytic drugs (specifically targeting senescent cells) and decipher the mechanism of aging, which is still poorly understood.
|17:35-18:00||Student Talk: Anwesha Barua
Title: Investigating the role of hepatocytes in fibrosis progression
Chronic liver diseases, irrespective of their etiology, progress through the same stages of fibrosis, cirrhosis, and hepatocellular carcinoma, if left untreated. Diagnostic techniques such as Transient Elastography have demonstrated an increase and decrease in liver stiffness during fibrosis progression and regression, respectively. These changes have been attributed to changes in the extracellular matrix (ECM). Studies on liver fibrosis have mainly focussed on the role of Hepatic Stellate Cells (HSCs) in fibrogenesis. On the other hand, hepatocytes, which perform many vital liver functions, were described as a ‘victim’ or ‘innocent bystander’. We hypothesize a more dominant role of hepatocytes in fibrogenesis, as an ‘accomplice’ or ‘perpetrator’.
Our goal is to understand how hepatocytes behave differently in the altered mechanical microenvironment in a fibrotic or cirrhotic liver and find a correlation between its stiffness and liver function. We are investigating how hepatocytes may assist HSCs in fibrogenesis, from a biomechanics perspective. We have developed an ex vivo model to simulate the progression and regression of fibrosis by fabricating polyacrylamide gels of stiffness mimicking the stiffness of a healthy (2-6 kPa), fibrotic (8-12 kPa), and cirrhotic (20-50 kPa) liver. We have observed changes in the proliferation rate and morphology of hepatocytes when cultured on different gels. The cells proliferate more and have a flat, well-spread morphology when grown on stiffer gels. Using Atomic Force Microscopy, we have determined the apparent modulus of elasticity of the cells on the different gels and also looked into the gene expression levels of specific proteins to derive a correlation between the hepatocyte’s stiffness and functionality. We are currently standardizing co-culture of hepatocytes and HSCs on the gels.
|Session 3: Systems Biology||10:15-10:55||Dr. Rukmini Kumar
Title: QSP in pharma R&D: quantitative, integrative approaches mitigate risk in drug development
|11:00-11:40||Prof. Karthik Raman
Title: Unravelling microbial interactions in the gut microbiome through computational approaches
Microorganisms are ubiquitous and exist in evolutionarily and metabolically diverse communities around us. In practically every ecosystem, microbes form complex dynamic assemblages—such as in the human gut where they outnumber human cells. Community structure in these microbiomes is dictated by a complex web of interactions, where metabolic interactions are known to predominate. In this study, we employ computational tools to interrogate community metabolic networks, to unravel the dependencies that exist between microbes in the gut. We used 52 important and commonly occurring microbial species in the gut, as identified in previous studies. We applied our previously developed graph-based computational framework, MetQuest, to identify the metabolic exchanges and the associated biosynthetic pathways between 1326 pairs of organisms. We also show how synergistic interactions can help in enhancing the amino acid biosynthesis in gut bacteria. Further, we computed a Metabolic Support Index, which captures the extent of support/interaction between a pair of microbes, based on the incremental change in metabolic capabilities achieved in a community vis-à-vis the individual organisms. We show that the gut organisms are arranged in multiple trophic levels, where a select few of them act as “hubs” of interaction. We also identified several metabolic exchanges between the gut organisms. These results, taken together, help us better understand the mechanism behind these interactions, which would pave the way for rational design of pre- and pro-biotic formulations
|11:40-12:05||Student Talk: H A S Shri Kishore
Title: Mechanisms of phenotypic plasticity in cancer metastasis
Metastasis, the process of cancerous cells invading multiple organs of the body, causes more than 90% of cancer-related deaths. No unique mutations could be associated with metastasis, and no cancer treatment so far can target metastasis. Recent studies suggest that metastasis is driven mainly by multiple interdependent axes of phenotypic plasticity, such as metabolic plasticity, drug resistance, dormancy, stemness, and Epithelial-mesenchymal plasticity (EMP). In particular, EMP – a developmental axis of phenotypic plasticity – is believed to be crucial for metastasis as it imparts the adherence and migratory characteristics to cancerous cells. Despite extensive physicochemical investigations, the mechanisms of the emergence of such phenotypic plasticity are still not understood. To understand these mechanisms, we take a two-pronged approach. On the one hand, we study the regulatory network topologies underlying EMP to identify characteristics that can give rise to plasticity. On the other hand, we construct models based on population dynamics data to understand the dynamics of switching and infer phenotypic plasticity mechanisms other than network topology, such as stochasticity, ecological interactions between various EMP phenotypes, and epigenetics. So far, our results suggest that the EMP networks have a higher fraction of positive feedback loops, which can give rise to phenotypic plasticity. Furthermore, small perturbations that reduce the number of positive feedback loops and increase the number of negative feedback loops can reduce phenotypic plasticity over a large parameter space. In my talk, I will be presenting a summary of these results together with the predictions from population dynamics models and how these two studies together lead us towards a better understanding of EMP.
|12:05-12:30||Student Talk: Subbalakshmi A R
TItle: NFATc acts as a non-canonical phenotypic stability factor for a hybrid epithelial/mesenchymal phenotype
Metastasis remains the cause of over 90% of cancer-related deaths. Cells undergoing metastasis use phenotypic plasticity to adapt to their changing environmental conditions and avoid therapy and immune response. Reversible transitions between epithelial and mesenchymal phenotypes – epithelial–mesenchymal transition (EMT) and its reverse mesenchymal–epithelial transition (MET) – form a key axis of phenotypic plasticity during metastasis and therapy resistance.
Recent studies have shown that the cells undergoing EMT/MET can attain one or more hybrid epithelial/mesenchymal (E/M) phenotypes, the process of which is termed as partial EMT/MET. Cells in hybrid E/M phenotype(s) can be more aggressive than those in either epithelial or mesenchymal state. Thus, it is crucial to identify the factors and regulatory networks enabling such hybrid E/M phenotypes. Here, employing an integrated computational-experimental approach, we show that the transcription factor nuclear factor of activated T-cell (NFATc) can inhibit the process of complete EMT, thus stabilizing the hybrid E/M phenotype. It increases the range of parameters enabling the existence of a hybrid E/M phenotype, thus behaving as a phenotypic stability factor (PSF). However, unlike previously identified PSFs, it does not increase the mean residence time of the cells in hybrid E/M phenotypes, as shown by stochastic simulations; rather it enables the co-existence of epithelial, mesenchymal and hybrid E/M phenotypes and transitions among them. Clinical data suggests the effect of NFATc on patient survival in a tissue-specific or context-dependent manner. Together, our results indicate that NFATc behaves as a non-canonical PSF for a hybrid E/M phenotype.
|Lunch Break||12:40-13:45||Lunch Break|
|Session 4: Biomedical Systems||13:50-14:30||Prof. Laoise McNamara
Title: Mechanobiologically mimetic model systems for study of Bone disease
Biophysical stimuli are as crucial as genes and biochemical signalling for bone development and function, from the earliest embryo and throughout life. Mechanobiology integrates engineering mechanics with cell and molecular biology to study these processes. Our research seeks to understand the role of mechanobiological processes in the disease of osteoporosis. Specifically, we have found that osteoblast and osteocyte mechanotransduction are fundamentally altered during estrogen deficiency. Furthermore, osteoblasts and osteocytes that have experienced estrogen withdrawal produce paracrine factors that exacerbate osteoclast resorption. These changes may play an important role in the overall disease progression, but are not yet fully understood and so no therapy has been developed to address them.
Most current understanding of bone pathophysiology has been derived either using 2D cell culture, which does not represent the complexity of in vivo biophysical cues, wherein bone cells are embedded within a 3D matrix and are simultaneously influenced by daily biophysical cues. Such approaches cannot fully capture, or account for both human biological and mechanical factors, and our research seeks to address this challenge. We develop advanced models that incorporate 3D multicellular niches within biomaterial matrices and use our custom bioreactors to achieve mechanically mimetic constructs and recreate in vivo loading. These novel in vitro models are applied to investigate the mechanisms underpinning changes in bone cells during osteoporosis and metastatic bone disease
|14:35-15:15||Prof. Rinti Banerjee
Title: Biomaterial strategies for drug delivery & beyond: innovations, translation & impact
Drug delivery strategies have the potential to increase the bioavailability of drugs and penetrate across anatomical barriers to reach deeper target tissues. Biodegradable and trigger responsive biomaterials act as platforms for the design of efficient drug delivery carriers. Biomimetic, trigger responsiveness, nanosize based penetration, site specific self assembly and sol gel transitions act as platform strategies to design smart biomaterials specifically suited for drug delivery in various systems. Several examples of these strategies and their translation will be covered in the talk. Amphiphilic phospholipid nanovesicles mimic the pulmonary surfactant and can be optimised to form respirable aerosols with deep penetration into the alveoli with non-invasive nebulisation techniques. These act as platforms for anti-oxidant, anti-inflammatory and anticancer drugs with synergistic pulmonary surfactant actions for therapy in acute respiratory distress syndrome and pulmonary metastasis respectively. Transdermal delivery requires strategies to pass through the ceramide rich stratum corneum barrier. Nanoparticles of fluidising phospholipids and fatty acids can be modulated to alter bilayer packing and act as platforms to pass through the stratum corneum, or pass along the follicular route for dermal and systemic effects. Stabilisation of the platform in oils have led to micronutrient loaded infant massage oils containing multivitamins and iron for neonatal development, leveraging traditional practices of infant massage with nanotechnology. Nanoparticle in biopolymeric microneedle platforms having conical morphology pass through the stratum corneum to form dermal depots for sustained release of drugs. Ultrasound responsive biomaterials consisting of sulphur hexafluoride loaded microbubbles linked to drug loaded lipopolymeric nanoparticles undergo cavitation in the presence of an ultrasound trigger. This phenomenon can be utilised for triggered drug release while the contrast enhancing property produces theranostic advantages for site specific therapy in cancers. Another barrier for drug delivery to the central nervous system is the blood brain barrier. Nanoparticle in slow degrading amphiphilic in situ gels act as depot formulations for post surgical delivery of chemotherapeutics in glioblastoma with minimal systemic accumulation. The urothelium of the urinary bladder poses another challenge to delivery of drugs to the urinary bladder. Intravesical delivery is limited by decreased retention and urinary excretion and poor penetration through the urothelium. Nanoparticle in in situ gels which are stable in variable pH and in the presence of urine are optimised for enhanced penetration through the urothelium. The platforms have potential in superficial bladder carcinoma, deep muscle penetrating stages and interstitial cystitis for enhanced effectiveness over several weeks. Core shell trigger responsive nanoparticles for posterior segment ocular drug delivery and for sequential delivery of multiple drugs are also explored. Nanocomposite gels have been developed that act as quick hemostatic, multifunctional agents for trauma care with hemostatic, antibacterial and wound healing properties. The talk will highlight some of these technologies, the strategies underlying the innovations and their translation.
|15:20-15:45||Student Talk: Neha Padillaya
Title: Biophysics of cell substrate interactions under shear
|16:00-16:25||Student Talk: Vishal Gupta
Title: A collagen-based macrophage infection model for studying host-pathogen interaction and drug efficacy in tuberculosis
In October 2020, the World Health Organization (WHO) reported 10 million new cases of tuberculosis (TB), which resulted in 1.4 million deaths, making it the leading cause of death in the world from infectious diseases. Mycobacterium tuberculosis (Mtb) is an obligate human pathogen and has the remarkable ability to survive in host macrophages. The bacteria encounter resident macrophages upon reaching the alveolus of hosts. The signalling by these infected host cells results in monocytes reaching the site of inflammation to contain the bacteria, which eventually leads to the formation of a granuloma.
In vitro Mtb infection experiments have been mostly carried out in two-dimensions (2D) on tissue culture polystyrene, using primary human monocytes, bone-marrow-derived macrophages (BMDMs), THP-1 monocytes among others. These studies have contributed a lot to our understanding of complex processes such as the arrest of phagosomal maturation, activation of innate immune responses, and how the various cell death pathways are modulated. However, monolayer culture is not a natural environment for the cells as the cells are subjected to very stiff surfaces and many cellular processes are dysregulated. Hence the results obtained are often difficult to translate. Several clinical trials for potential TB drugs and treatment regimen have failed despite their promise in the initial stage of testing. This suggests that there is a need to develop better models to study host-mycobacteria interaction.
Therefore, in recent years, three-dimensional (3D) in vitro models have gained rapid interest in the field. The advantage of a 3D model is that it is a more realistic representation of human tissues outside our bodies. Among the various 3D platforms, hydrogels – which are a network of hydrophilic polymers and have the ability to hold a large amount of biological fluids are an ideal choice to be used as tissue mimic
We have engineered collagen hydrogels using collagen I, which is the primary extracellular component present in the human lungs. We have found that both 1 mg/mL and 2 mg/mL collagen hydrogels have a micromechanical environment that is similar to human lung tissue. These gels support the culture of THP-1 monocytes and the cells can survive Mtb infection for a long duration. The THP-1 monocytes in the infected gels differentiate to macrophages and accumulate lipid bodies, a phenotype regularly observed in human TB granulomas. Further studies have shown that the first line tuberculosis drugs are effective in reducing the bacterial load and hence it can be a suitable model to test new TB drugs.
|Panel Discussion and Closing Ceremony||16:30-17:30||Shifting goalposts: Research in a post-COVID-19 world|
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