Calendar of MRSEC Events

The CMSA will host the ninth annual Conference on Big Data. The 2023 Big Data Conference features speakers from the Harvard community as well as scholars from across the globe, with talks focusing on computer science, statistics, math and physics, and economics.

Organizers: Michael Douglas, CMSA, Harvard University; Yannai Gonczarowski, Economics and Computer Science, Harvard University; Lucas Janson, Statistics and Computer Science, Harvard University; Tracy Ke, Statistics, Harvard University; Horng-Tzer Yau, Mathematics and CMSA, Harvard University; Lu Yue, Electrical Engineering and Applied Mathematics, Harvard University.

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Registration is required.

Chuanhua Duan, Boston University
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: TBD

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Jiliang Hu, MIT
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: TBD

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Jacques Fattaccioli, Paris Sciences et Lettres University
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: Response to pathogens and homeostasis is orchestrated by the complex interactions and activities of the large number of diverse cell types involved in the immune response. The innate immune response occurs soon after pathogen exposure and is carried out by phagocytic cells such as neutrophils or macrophages. The subsequent adaptive immune response involves antigen-presenting cells such as macrophages or dendritic cells; and antigen stimulation-dependent cell types such T cell subsets and B cells. As an alternative to polymers or hydrogels that are commonly used when model substrates are needed for uptake or migration studies from the point of view of mechanobiology, we developed ligand-functionalized lipid droplets to address these questions. In this talk, I will present how to make and characterize functional lipid droplets, how they can be used in the context of phagocytosis, cell migration and antigen extraction, and I will present the most recent ongoing results.

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Derin Sevenler, Massachusetts General Hospital, Department of Surgery
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: Intracellular delivery of biomolecules or nanomaterials is a critical step in many bioengineering processes across applications in science, technology, and medicine. In particular, emerging cell and gene therapies can require the genetic manipulation of extremely large numbers of cells (hundreds of trillions of cells, in some cases), and scale-up of conventional methods for delivering genetic material or gene editing complexes into cells (viral vectors, cationic polymers, electroporation) have faced issues with efficiency and/or cytotoxicity. In this talk, we will describe recent work developing a high-throughput method of intracellular delivery which used viscoelastic flow forces within a microfluidic chip to stretch and temporarily permeabilize the plasma membrane of cells, thereby enabling rapid and efficient delivery of large biomolecules including proteins, nucleic acids, and CRISPR-Cas ribonucleoprotein complexes to the cytosol. This method was notably fast, processing over 250 million cells per minute in a single microchannel (100x-1,000x faster than comparable methods) with up to 95% delivery efficiency. Altogether, viscoelastic mechanoporation seems to be a feasible method for high-throughput intracellular delivery for a range of different cell types that includes primary T and NK cells.

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Sahand Hormoz (Harvard Medical School, Dana-Farber Cancer Institute)
1:00pm EST | 20 Garden Street, Room G10, Cambridge, MA and VIRTUAL

Abstract:
Two recent projects from my lab that involve lineage trees of cells (the branching diagram that represents the ancestry and division history of individual cells). In the first project, we reconstructed the lineage trees of individual cancer cells from the patterns of randomly occurring mutations in these cells. We then inferred the age at which the cancer mutation first occurred and the rate of expansion of the population of cancer cells within each patient. To our surprise, we discovered that the cancer mutation occurs decades before diagnosis. For the second project, we developed microfluidic 'mother machines' that allow us to observe mammalian cells dividing across tens of generations. Using our observations, we calculated the correlation between the duration of cell cycle phases in pairs of cells, as a function of their lineage distance. These correlations revealed many surprises that we are trying to understand using hidden Markov models on trees. For both projects, I will discuss the mathematical challenges that we have faced and open problems related to inference from lineage trees.

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Neel Joshi, Northeastern University
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: The intersection between synthetic biology and materials science is an underexplored area with great potential to positively affect our daily lives, with applications ranging from manufacturing to medicine. My group is interested in harnessing the biosynthetic potential of microbes, not only as factories for the production of raw materials, but as fabrication plants that can orchestrate the assembly of complex functional materials. We call this approach “biologically fabricated materials”, a process whose goal is to genetically program microbes to assemble materials from biomolecular building blocks without the need for time consuming and expensive purification protocols or specialized equipment. Accordingly, we have developed Biofilm Integrated Nanofiber Display (BIND), which relies on the biologically directed assembly of biofilm matrix proteins of the curli system in E. coli. We demonstrate that bacterial cells can be programmed to synthesize a range of functional materials with straightforward genetic engineering techniques. The resulting materials are highly customizable and easy to fabricate, and we are investigating their use for practical uses ranging from bioremediation and biodegradable bioplastics to engineered therapeutic probiotics.

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Since its inception in 2004, the Microbial Science Initiative has sponsored and hosted an annual symposium for those in the Harvard and greater Boston communities. The spring event showcases magnificent research across a breadth of microbe-centric topics spanning environmental and biomedical sciences. The MSI Symposium is $20 for the public or $5 for students & postdocs. Welcome to the microbial world! Mid-morning and mid-afternoon breaks with refreshments will be provided, and there will be a 75 minute break for lunch mid-day.

Ticket registration required, $20 or $5 for Students & Postdocs, and is open to the public

Mehran Kardar, MIT
1:00pm EST | 20 Garden Street, Room G10, Cambridge, MA and VIRTUAL

Abstract:
When competing species grow into new territory, the population is dominated by descendants of successful ancestors at the expansion front. Successful ancestry depends on the reproductive advantage (fitness), as well as ability and opportunity to colonize new domains. (1) Based on symmetry considerations, we present a model that integrates both elements by coupling the classic description of one-dimensional competition (Fisher equation) to the minimal model of front shape (KPZ equation). Macroscopic manifestations of these equations on growth morphology are explored, providing a framework to study spatial competition, fixation, and differentiation, In particular, we find that ability to expand in space may overcome reproductive advantage in colonizing new territory. (2) Variations of fitness, as well as fixation time upon differentiation, are shown to belong to distinct universality classes depending on limits to gain of fitness.

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Meni Wanunu, Northeastern University
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: Nanopores have gained a lot of attention recently for their ability to sequence nucleic acids. Recently, however, a surge of interest in the use of nanopores for analyzing proteins has been witnessed. I will talk about two approaches that our lab has taken for characterizing proteins. First, I will describe a method for full-length single-file protein translocation and discrimination using a biological pore. Second, I will describe a method for probing conformational states of a protein and its electrical unfolding. With these tools in mind, it is exciting to think about possibilities in using nanopores for studying protein variants, post-translational modifications, and interactions of proteins with small molecule drugs.

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Sulin Zhang, Pennsylvania State University, Department of Engineering Science and Mechanics
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: In various electro/biochemical processes, mechanical stress generation and transmission pathways exist in parallel and interact in concert with chemical reaction and mass diffusion pathways. How might the mechanics-electrochemistry reciprocity be harnessed for energy storage and energy harvesting, and unharnessed in battery degradation? Similarly, how might the mechanics-biochemistry crosstalk be regulated in development and repair, and dysregulated in disease and injury? These questions have been stimulating new understanding at the interfaces between mechanics and other disciplines including materials, chemistry, biology, and medicine. In this talk, I will show a set of exciting phenomena in rechargeable batteries and living organisms to highlight the crosstalks. Emphasis will be placed on the fundamental mechanics linking to bio/electrochemistry, which underlies materials design, energy storage and harvesting, disease control, and nanomedicine innovation.

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Hemanoel Passareli, Visiting Scholar to Hanage Lab
12-1pm EST | 24 Oxford Street, Room 375 - Classroom 375, Cambridge, MA

Pangenome analysis has become a vital tool to understand bacterial diversity. In this Chalk Talk, we will discuss how we can interpret a pangenome from an ecological perspective to explore the evolution of microorganisms.

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Shane McInally, Brandeis University
1:00pm EST | 20 Garden Street, Room G10, Cambridge, MA and VIRTUAL

Abstract:
The sizes of many subcellular structures are coordinated with cell size to ensure that these structures meet the functional demands of the cell. In eukaryotic cells, these subcellular structures are often membrane-bound organelles, whose volume is the physiologically important aspect of their size. Scaling organelle volume with cell volume can be explained by limiting pool mechanisms, wherein a constant concentration of molecular building blocks enables subcellular structures to increase in size proportionally with cell volume. However, limiting pool mechanisms cannot explain how the size of linear subcellular structures, such as cytoskeletal filaments, scale with the linear dimensions of the cell. Recently, we discovered that the length of actin cables in budding yeast (used for intracellular transport) precisely matches the length of the cell in which they are assembled. Using mathematical modeling and quantitative imaging of actin cable growth dynamics, we found that as the actin cables grow longer, their extension rates slow (or decelerate), enabling cable length to match cell length. Importantly, this deceleration behavior is cell-length dependent, allowing cables in longer cells to grow faster, and therefore reach a longer length before growth stops at the back of the cell. In addition, we have unexpectedly found that cable length is specified by cable shape. Our imaging analysis reveals that cables progressively taper as they extend from the bud neck into the mother cell, and further, this tapering scales with cell length. Integrating observations made for tapering actin networks in other systems, we have developed a novel mathematical model for cable length control that recapitulates our quantitative experimental observations. Unlike other models of size control, this model does not require length-dependent rates of assembly or disassembly. Instead, feedback control over the length of the cable is an emergent property due to the cross-linked and bundled architecture of the actin filaments within the cable. This work reveals a new strategy that cells use to coordinate the size of their internal parts with their linear dimensions. Similar design principles may control the size and scaling of other subcellular structures whose physiologically important dimension is their length.

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12-1pm EST | 24 Oxford Street, classroom #375, Cambridge, MA

Is there an item that's been languishing on your to-do list? Do you have an assignment to do and just can't harness the motivation to take the first step? Register and join the Microbial Sciences Initiative for a Micro-Goal Lunch Hour! Open to all Harvard students and postdocs, especially those with an interest in the microbial world.

Neel Joshi, Northeastern University
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: TBD

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Mark Bowick, Kavli Institute for Theoretical Physics, UCSB
1:00pm EST | 20 Garden Street, Room G10, Cambridge, MA and VIRTUAL

Abstract:
Motivated by the existence of membrane-less compartments in the chemically active environment of living cells, I will discuss the dynamics of droplets in the presence of active chemical reactions. Therefore, I will first introduce the underlying interplay between phase separation and active reactions, which can alter the droplet dynamics compared to equilibrium systems. A key feature of such systems is the emergence of concentration gradients even at steady states. In the second part of this talk, I will discuss how these gradients can trigger instabilities in the core of chemically active droplets, giving rise to a new non-equilibrium steady state of liquid spherical shells. Finally, I will present experimental and theoretical results discussing the existence and energetic cost of this non-equilibrium steady state in a coacervate system.

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Brandy Toner
4 - 5pm EST | William James Hall, Room 105, 33 Kirkland Street, Cambridge, MA

TBD

Bryan Spring, Northeastern University, Dept. of Physics
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: This talk will introduce concepts of targeted photodynamic therapy with microscale fidelity using clinical antibody–photosensitizer (benzoporphyrin derivative monoacid A, verteporfin) conjugates. These initially quenched (“off”) photoimmunoconjugates target tumor cell-surface biomarkers and become activated upon cell-internalization ("on"). Present efforts to further develop these concepts for precision treatment of heterogenous human ovarian cancer will be discussed.

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Invited Speakers:
Corey O'Hern, Yale University
Leslie Shor, University of Connecticut
Ian Wong, Brown University
Evan Wujcik, University of Maine

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Jonathan Bauermann, Max Planck Institute for the Physics of Complex Systems
1:00pm EST | VIRTUAL

Abstract:
Morphogenesis, the process through which genes generate form, establishes tissue scale order as a template for constructing the complex shapes of the body plan. The extensive growth required to build these ordered substrates is fueled by cell proliferation, which, naively, should disrupt order. Understanding how active morphogenetic mechanisms couple cellular and mechanical processes to generate order remains an outstanding question in animal development. I will review the statistical mechanics of orientational order and discuss the observation of a fourfold orientationally ordered phase (tetratic) in the model organism Parhyale hawaiensis. I will also discuss theoretical mechanisms for the formation of orientational order that require both motility and cell division, with support from self-propelled vertex models of tissue. The aim is to uncover a robust, active mechanism for generating global orientational order in a non-equilibrium system that then sets the stage for the development of shape and form.

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Carla Fernandez-Rico, ETH Zurich
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: TBD

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Alexis Jaramillo Cartagema
12-1pm EST | 24 Oxford Street Room 375, Classroom 375, Cambridge, MA

12-1pm EST | 24 Oxford Street, classroom #375, Cambridge, MA

Is there an item that's been languishing on your to-do list? Do you have an assignment to do and just can't harness the motivation to take the first step? Register and join the Microbial Sciences Initiative for a Micro-Goal Lunch Hour! Open to all Harvard students and postdocs, especially those with an interest in the microbial world.

Xin Zhao, Hong Kong Polytechnic University
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: Photocrosslinkable polymers are polymers that can be solidified from liquid upon light exposure. They have been employed to fabricate tissue engineered constructs due to the mild conditions for crosslinking, highly tunable mechanical and structural modifiability, printability, biodegradability and biocompatibility. These biomaterials can maintain their structural integrity after biofabrication and provide topological, biochemical, and physical cues to guide cellular behaviors by creating a biomimetic microenvironment.

The emphasis of this talk is placed on how photocrosslinkable polymers can be used to achieve tissue regeneration, for example, their fabrication into various scaffolds (electrospun fibers, microspheres, and 3D printed scaffolds) to reconstruct bones. Specifically, assisted by microfluidics, we have developed photocrosslinkable methacrylated gelatin (GelMA) based microspheres encapsulating human mesenchymal stem cells (MSCs) for bone repair. Due to the mild crosslinking conditions, we found that the GelMA microspheres can provide a favourable micro-environment for MSC survival, spreading, migration, proliferation and osteogenesis. In another study, we prepared a periosteum mimicking bone aid (PMBA) by electrospinning photocrosslinkable GelMA with L-arginine-based unsaturated poly(ester amide) (Arg-UPEA), and methacrylated hydroxyapatite nanoparticles (nHAMA). Upon light exposure, the resultant hydrogel fibrous scaffolds can solidify within seconds. Via controlling the crosslinking density, we can control the scaffolds’ mechanical and degradation property. The optimal scaffold was found to provide long term structural and functional support and mediation of physiological activity. With the aid of 3D printing, we developed 3D bone scaffolds made of photocrosslinkable nanocomposite ink consisting of tri-block poly (lactide-co-propylene glycol-co-lactide) dimethacrylate (PmLnDMA, m and n respectively represent the unit length of propylene glycol and lactide) and nHAMA. It is discovered that nHAMA can rapidly interact with PmLnDMA upon light exposure within 140 seconds and form an inorganic-organic co-crosslinked nanocomposite network. This bone ink was found to provide good mechanical support and bioactivity (allow for encapsulation and long-term release of growth factors) for bone regeneration.

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Beau Schaeffer
12-1pm EST | 24 Oxford Street Room 375, Classroom 375, Cambridge, MA

Yu Qiu, Department of Earth, Atmospheric, and Planetary Sciences, MIT
6 - 7:30pm | Pierce Hall 209, 29 Oxford Street

Abstract: The displacement of one fluid by another immiscible fluid in confined geometries occurs in many natural and industrial settings from geological CO₂ sequestration to microfluidics. The fluid-solid interactions are key to understanding the combined effects of wetting, capillarity and viscous forces, which, in turn, control the fluid-fluid displacement patterns. One fundamental aspect of fluid-fluid displacement in confined geometries is the wetting transition: the displacement rate above which films of the defending fluid are deposited on the confining surfaces. These films may later dewet, giving rise to complex “residual fluid” patterns. Earlier experiments in our group have shown that the wetting transition results in interface pinch-off that generates disconnected bubbles and drops even in uniform capillaries without external crossflow (Zhao et al., PRL 2018). Here I will present a phase-field model to simulate the two-phase flow with moving contact lines and investigate the interface dynamics in a smooth confinement over a wide range of wettability conditions and viscosity contrast. I will show that the pinch-off of a bubble only occurs when the invading fluid is less viscous. Since real surfaces are rough, we investigate the role of wall roughness on two-phase displacements in confined geometries by means of experiments on a microfluidic fracture with precisely-controlled structured surface. We show that the roughness induces two types of liquid films entrained on the solid surfaces: the classical Bretherton “thick film”, and a new type of “thin film” that is confined within the roughness. Each type is characterized by distinct stability criteria and dewetting dynamics. Our work shed light on the microscale physics and macroscopic displacement patterns in confined geometries that may control long-term biogeochemical reactions.

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Jörn Dunkel, MIT
1:00pm EST | VIRTUAL

Abstract:
Over the last two decades, major progress has been made in understanding the self-organization principles of active matter. A wide variety of experimental model systems, from self-driven colloids to active elastic materials, has been established, and an extensive theoretical framework has been developed to explain many of the experimentally observed non-equilibrium pattern formation phenomena. Two key challenges for the coming years will be to translate this foundational knowledge into functional active materials, and to identify quantitative mathematical models that can inform and guide the design and production of such materials. Here, I will describe joint efforts with our experimental collaborators to realize self-growing bacterial materials [1], and to implement computational model inference schemes for active and living systems dynamics [2,3].

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Andee Wallace
4 - 5pm EST | William James Hall, Room 105, 33 Kirkland Street, Cambridge, MA

The World Health Organization estimates that agricultural productivity will need to increase by 70% by 2050 to meet the food needs of a global population of 10B people. Facing a changing climate and increasing disease pressure, growers today spend nearly $80B on six billion pounds of pesticides each year, and yet still experience yield losses of 20-40% due to pests and disease. Broad-acting, chemically derived pesticides - currently the industry standard - are losing both efficacy and public support as resistance spreads and their negative environmental impacts become clear. At Robigo, we believe in building on nature’s foundation to engineer solutions that work for growers, consumers, and the environment. We have developed a scalable plug and play platform technology that leverages synthetic biology, CRISPR, and data science to engineer microbes that are naturally found out in the fields to protect crops, fight disease, and improve overall yields. Initially targeting three diseases that affect citrus, apples, and tomatoes, our microbes outperform commercial chemical pesticides and reduce disease by over 90% while increasing plant biomass by over 15%. Robigo is unlocking the potential of engineered microbes in agriculture to fundamentally change how the world grows food and create a more sustainable future for agriculture. Founded by MIT synthetic biologists, Robigo is a VC-backed, Seed-stage biotech startup based in Cambridge, MA.

Qiong Zhang, Department of Mechanical Engineering, MIT
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

Abstract: Sediment transport caused by particles rolling, sliding, and hopping on a river bed is called bedload transport. Semi-empirical formulas to predict bedload sediment flux from the driving factors, known as the transport relation, can be highly inaccurate. Simulations where the sediment particles are fully resolved are carried out to find if the predictions can be improved by considering more particle parameters. After being validated against flume experiments, the numerical scheme is used to simulate bedload transport under many conditions, and its results show that at a fixed relative hydrodynamic driving force, varying river slope (on gentle slopes), fluid depth, mean particle size, particle surface sliding friction coefficient, and grain-grain damping coefficient cause almost no variation of the transport rate. The simulations also shed light on the microscopic mechanisms such as how the fluid torque on particles helps initiate rolling and subsequent grain transport. We further use the numerical scheme to guide development of an alternative framework that can predict the flow profiles for the fast transport as well as the gradual transport beneath the bed surface without resolving the individual particles, which is a more tractable way to model large-scale bedload sediment transport problems.

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Nazim Bouatta, Harvard Medical School
3:30-5:00pm EST | 20 Garden Street Room G10, Cambridge, MA and VIRTUAL

Thursday, February 9, Lecture 1:
A brief intro to protein biology. AlphaFold2 impacts on experimental structural biology. Co-evolutionary approaches. Space of ‘algorithms’ for protein structure prediction. Proteins as images (CNNs for protein structure prediction). End-to-end differentiable approaches. Attention and long-range dependencies. AlphaFold2 in a nutshell.

Thursday, February 16, Lecture 2:
AlphaFold2 architecture. Turning the co-evolutionary principle into an algorithm: EvoFormer. Structure module and symmetry principles (equivariance and invariance). OpenFold: retraining AlphaFol2 and insights into its learning mechanisms and capacity for generalization. Applications of variants of AlphaFold2 beyond protein structure prediction: AlphaFold Multimer for protein complexes, RNA structure prediction.

Thursday, March 9, Lecture 3:
Limitations of AlphaFold2 and evolutionary ML pipelines. Current single sequence models. Protein language models (LM): single sequence + LM embeddings. Combining LM models with Frenet-Serret construction for protein structure prediction. Applying AlphaFold2 and OpenFold for language models.

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12-1pm EST | 24 Oxford Street, classroom #375, Cambridge, MA

Is there an item that's been languishing on your to-do list? Do you have an assignment to do and just can't harness the motivation to take the first step? Register and join the Microbial Sciences Initiative for a Micro-Goal Lunch Hour! Open to all Harvard students and postdocs, especially those with an interest in the microbial world.

Amin Doostmohammadi, Niels Bohr Institute, University of Copenhagen
1:00pm – 2:30pm (EST) | VIRTUAL or 20 Garden St, seminar room G-10

Abstract: I will focus on the interaction between different active matter systems. In particular, I will describe recent experimental and modeling results that reveal how interaction forces between adhesive cells generate activity in the cell layer and lead to a potentially new mode of phase segregation. I will then discuss mechanics of how cells use finger-like protrusions, known as filopodia, to interact with their surrounding medium. First, I will present experimental and theoretical results of active mirror-symmetry breaking in subcellular skeleton of filopodia that allows for rotation, helicity, and buckling of these cellular fingers in a wide variety of cells ranging from epithelial, mesenchymal, cancerous and stem cells. I will then describe in-vivo experiments together with theoretical modeling showing how during embryo development specialized active cells probe and modify other cell layers and integrate within an active epithelium.

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Douglas H. Bartlett, PhD, UC San Diego
4 - 5pm EST | William James Hall, Room 105, 33 Kirkland Street, Cambridge, MA

A major portion of microbial life on Earth is present in low-temperature/deep-sea environments, and yet much remains to be learned of their diversity, adaptations and activities. Studies of these microbes in situ and ex situ is providing fundamental and biotechnological insights, and will be critical to many possible ocean-based decarbonization processes. In this presentation I will first discuss what we have learned about proteomes and cell envelopes of piezophilic (high pressure-adapted) isolates. Then I will transition to investigations of deep-sea microbial activities using pressure-retaining seawater sampling to collect microbes with minimal temperature/pressure alteration, followed by the sorting and identification of cells active under in situ deep-sea conditions. One aspect of this work is the indication that certain microbial groups (e.g., members of the Thaumarchaeota) are highly sensitive to decompression/incubation effects, reducing their perceived significance when collected using standard methods.
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