Cell Biology & Physiology Seminar with Mouzhe Xie on Diamond-Based Quantum Sensor for Molecular Analytics

Quantum sensing technologies enable some of the most precise measurements that human beings have ever achieved. In recent years, optically addressable nitrogen-vacancy (NV) color center hosted by diamond crystal has been used as a novel quantum sensor, which has exquisitely sensitive response to local magnetic field fluctuations. It is therefore capable to perform micro-/nano-scale NMR experiments, manifesting enormous potential to study biological systems on extremely small sample volume – even down to single-molecule regime. In this seminar, I will discuss some of the comprehensive efforts to develop NV-based quantum sensing platforms for a wide range of applications in chemistry and biology. I will start with a general introduction to quantum sensing followed by conventional NMR spectroscopy as a powerful tool to study biomolecules, as well as their connections to the NV-based nanoscale NMR. I will then introduce a biocompatible surface functionalization architecture for interfacing a diamond quantum sensor with individual intact biomolecules under physiological conditions. A sensing modality based on diamond membrane integrated with flow channel will also be discussed, which is a promising platform for a variety of experiments at molecular, cellular, and even living-organism levels. Finally, I will conclude by providing an outlook on how NV-based quantum sensing platforms, combined with other advanced spectroscopy and microscopy methods, can be utilized to address important biophysical and bioanalytical questions with unprecedented sensitivity and spatial resolution, which will enhance our understanding of molecular interactions and cellular processes and ultimately improve human health. 
 

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Biomedical Engineering Seminar with Thomas Boland on Cells in Machines

When we first described inkjet bioprinting (TIB) of cells in 2003, the devices were treated like a black-box.  Quantifying the input and measuring the output has become the hallmark of not only our group but, indeed, the entire field of bioprinting. Most of this is understandable, as it is virtually impossible to characterize cells that are inside the printing orifices, extrusion needles, or drops ejected from ribbons. Also understandable is then that we may be missing out on important information about cell biology, for example, what may be happening inside the printer or shortly after the bioprinting event. We will describe here some recent discoveries of cell behavior due to inkjet bioprinting.

For these experiments, we use primary adult dermal fibroblasts which were expanded for 2-3 passages upon receiving. The cells were harvested and resuspended in PBS and bioprinted into a 96-well plate with pluriSTEM media. Cells were then transferred either into precoated 96-well plates or 20 µL drops were pipetted for hanging drop culture using a multichannel pipettor. IPC to differentiation protocols was applied and the induction was begun approximately 45 mins after TIB for the cells that were transferred to the plate immediately after printing. When differentiating aggregates, the initiation happened 45 mins after the aggregates were transferred into the 96 wells. Preliminary results indicate that all cells expressed the 3 pluripotency markers oct-4, nanog, and sox-2. After differentiation protocols,  the cells stained positively for tropinin-3 for the cardiomyocyte differentiation protocol.  The cells also elongated and became more cardiomyocyte-like in their morphology.  We analyzed bulk RNA seq data and our preliminary results showed upregulation of some genes that have been implicated as stem cell markers: EPCAM, LEFTY1, ZFP42, and TEX19. In addition, differential expression of genes associated with pluripotency-relevant pathways show some pathways are off like the MAPK/p38, MAPK/JNK1-3 which would be expected for a pluripotent state, but at this time the activation of the hippo pathway is inconclusive with TAZ highly upregulated but YAP slightly downregulated. Similarly, GSK3B is off and TGFB1, LIF/PIK3, and AKT1 are on as expected for pluripotency, but SMAD2/3 and CTNNB1. Examining the gene network of upregulated genes, one can clearly distinguish the pivotal role of FOS, FOXO1, and PIK3 all related to pluripotency. In conclusion, bioprinted fibroblasts will at least temporarily adopt a more primitive or dedifferentiated state, reminiscent of pluripotency. While immunochemistry shows the classic transcription factors required for pluripotency, gene expression shows a more nuanced picture of the transformations that occur upon printing. Understanding these transformations, even if temporary will be crucial when trying to build tissues using bioprinting technologies.

Registration is required to attend virtually. Please register.

 

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Cell Biology & Physiology Seminar with Aldona Mzyk on Nanodiamond-Based Quantum Sensing in Cell Biology

Sparkling, hard and durable these are some of the properties commonly associated with diamonds. These qualities have made them desirable within our society for a centuries. In research, the unique properties of diamonds have drawn in many enthusiasts. Particularly, nanodiamonds with crystal lattice defects such as the negatively charged nitrogen-vacancy (NV^–) centers, which have emerged as a powerful and versatile quantum sensors for diverse quantities. This talk focuses on a specific way to use quantum-based sensing properties of nanodiamond with ensembles of NV^– centers, a technique called relaxometry (or T1). The key features of the NV⁻ center are its optically detectable and controllable spin states. In other words, the NV^– allows the conversion of magnetic noise into optical signals. Optical signals provide nanoscale resolution and unprecedented sensitivity as the detectability is far greater than that of direct magnetic noise detection. Analogously to T1 measurements in conventional magnetic resonance imaging (MRI), relaxometry allows the detection of different concentrations of paramagnetic species. However, relaxometry allows very local measurements, the detected signals are from nanoscale voxels around the NV^– center. Apart from detecting magnetic signals, responsive coatings can be applied to modify surface of nanodiamonds, which render T1 sensitive to other parameters as pH, temperature or electric fields.

Together with my colleagues from the UMCG in the Netherlands (group of prof. Romana Schirhagl) we were the first researchers to apply relaxometry to understand the multiple functions of free radicals (FR) in cell biology. FRs are omnipresent and one of the key players in the ageing process on a molecular level. Despite their relevance, information about FRs is sparse and therefore their use as clinical biomarkers is severely limited. Since FRs are short lived and reactive, it is challenging to detect them with the state of the art methodology. So far, I have proved that the nanodiamonds and T1 relaxometry technique could be used for the real-time monitoring of changes in the concentration of free radicals at the level of single human cells, yeasts and bacterial biofilm. In my talk I will address a few exciting examples of biological processes and their clinical relevance where the role of free radicals was explored with T1 relaxometry. In one of the projects, I have been investigating FRs generation in samples from arthritis patients. Arthritis is a common disease which is characterized by a decline of cartilage in joints. It can lead to disabilities and a diminished quality of life. The two most common types of arthritis are osteoarthritis (OA) where cartilage damage occurs in degenerative diseases and rheumatoid arthritis (RA) where the decline occurs during chronic inflammation of joints. I have found significant differences in the level of free radicals in RA and OA synovial fluids and derived cells. The proof-of-concept experiment has also shown that nanodiamond magnetometry enables real-time efficiency monitoring of anti-inflammatory therapeutics. Apart from the arthritis research, I have shown there is great potential in using nanodiamond magnetometry to investigate a free radical-based theory for male infertility. Herein, the unknown factor was the source of radicals that play a role in the sperm maturation process. The nanodiamond magnetometry allowed me to identify the prominent source of radical generation in sperm maturation and shed light on a role of progesterone.

Finally, with this talk I would like to stimulate discourse on the future of T1 relaxometry. I will give you insight into my further research ambitions and how these will open a new perspective for using nanodiamond-based quantum sensing to explore unknown aspects of oxidative stress in mechanobiology. This is especially important for the design of next generation biomaterials and drug delivery systems for modulation of immune responses in various organs.

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Cell Biology & Physiology Seminar with G. Edward Marti on New Transcriptomic and Imaging Tools to Track Trajectories of Aging and Disease

We are in a biological imaging and measurement revolution as tools are rapidly advancing our ability to measure proteins at the nanometer-scale, cells at the micron-scale, tissues at the millimeter-scale and beyond. There is an unmet need to improve longitudinal measurements of molecular and cellular changes inside living animals and witness key events in an organism’s response to aging and disease progression. I will present our efforts to study changes in cellular heterogeneity in aging mice with single-cell transcriptomics, and to enhance the time resolution of single-molecule experiments with novel imaging techniques.

Single-cell transcriptomic atlases are teaching us that a “cell type” is really a heterogeneous mixture of cells with a continuum of expression, yet it has long been contested how, or if, that heterogeneity changes with age. We developed a quantitative model of the measurement process from which we can identify genes with changing levels of biological noise from young adult to elderly mice. We find that genes involved in metabolism (specifically, oxidative phosphorylation) shows a ubiquitous decrease in noise and heterogeneity with age across disparate cell types and tissues.

Super-resolution imaging of bright nanoparticles enables us to track individual dynein molecular motors with a resolution of several nanometers and milliseconds. We are constructing a next-generation microscope towards angstrom localization in tens of microseconds to resolve record-fast dynamics of individual molecular motors and proteins. Furthermore, we are building a multimolecular platform with targeted microbubbles to image cellular changes by centimeters inside a living animal for days or weeks using ultrasound imaging.

 

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Biomedical Engineering Seminar with Nanyin Zhang on Investigating Brain Network Function

Resting-state functional magnetic resonance imaging (rsfMRI) provides a powerful tool to characterize the organizational architecture of whole-brain networks. However, several intrinsic issues have limited the potentials of rsfMRI from being fully realized. In this presentation I will discuss these issues, and demonstrate that they can be partially solved by integrating rsfMRI with cutting-edge neurotechnology such as optogenetics/chemogenetics, electrophysiology and behavioral methods, which allow multi-scale multi-dimensional information to be collected and modulated in rodent models.

Registration is required to attend virtually. Please register.

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Biomedical Engineering Seminar with Sarah Keller on Vacuole Membranes of Hungry Yeast

Liquid-liquid phase separation in living biological membranes is usually described as occurring on sub-micron length scales. A stunning counterexample occurs in S. cerevisiae. When the yeast shift from the log stage of growth to the stationary stage, huge, micron-scale liquid domains appear in the membranes of the vacuole, an endosomal organelle. These phases are functionally important, enabling yeast survival during periods of stress. This talk will review recent results showing: (1) This miscibility transition is reversible as would be expected from equilibrium thermodynamics, even though it occurs in a living system. (2) Yeast actively regulate this phase transition to hold the membrane transition ~15C above the yeast growth temperature. (3) In cases when domains appear as stripes, there is no current theory that explains all physical observables of the system. This research was conducted in collaboration with the labs of Alex Merz (University of Washington) and Robert Ernst (Universität des Saarlandes).

Registration is required to attend virtually. Please register.

 

 

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Exhibition on "Reaching New Heights: The Life and Legacy of Michael W. Friedlander"

In addition to his great commitment to his family and students, Friedlander was passionate about his research and protecting the greater St. Louis community. For nearly six decades, Friedlander educated, challenged, and inspired the lives he touched, and his efforts helped shape history locally and nationally. The Reaching New Heights exhibition celebrates Friedlander’s career and his legacy.

This exhibition was organized by Graduate Research Assistant Emily Alberts in partnership with the Museum Studies Heritage and Public History program at the University of Missouri-St. Louis.

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Introduction to Quantum Sensing Summer Boot Camp

Our summer boot camp will take place Monday July 10th through Friday July 14th from 9am-11am with flexible afternoons for hands-on labs. All activities will take place in Crow Hall, Physics Building on WashU Danforth Campus. This boot camp is available to graduate students.

Learning Objectives:

• Become comfortable with the "lingo" of quantum sensing
• Level the field for biologists, physicists, chemists, and engineers

Contact nrt-linq@wustl.edu for more information. The only prerequisite is to have taken a college-level physics course!

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She Leads Symposium @ WashU 2023

Past speaker highlights include Justice Sandra Day O’Connor, activist Tarana Burke, NASA scientist Moogega Cooper, First Lady Jill Biden, along with numerous scientists, entrepreneurs, professors, researchers, and community leaders from a variety of disciplines and backgrounds.

She Leads @ WashU provides a forum that enables and empowers women to lead in the 21st century. This year's event includes the Ida H. Early Composing a Life panel, sponsored by the Women's Society of Washington University.

This event, open to the public, connects fellows, students, alumni, faculty and community members through a variety of speakers, sessions and networking opportunities.  

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ESE Seminar with Adilson Motter on Scalable Control of Large Physical, Biological, and Socio-Technological Networks

Abstract: The control of large-scale networks is a pressing problem of relevance to numerous natural and engineered systems. Despite recent advances in network and control science, there has been a lack of fundamental understanding of the network properties that can enable efficient and effective control of such systems. In this presentation, I will introduce a notion of network locality and demonstrate that the property of being localized is common across numerous network systems. I will then show that this property can be exploited to dramatically improve our ability to control large-scale networks, including networks with nonlinear dynamics. Illustrative examples will include synchronization dynamics in the Eastern US power grid, epidemic spreading mediated by the global air-transportation network, and Alzheimer’s disease dynamics in a human brain network. Our results establish that large networks can be controlled with computation and communication costs comparable to those of small networks.

Reference: C. Duan, T. Nishikawa, and A.E. Motter,  Prevalence and scalable control of localized networks,  Proc. Natl. Acad. Sci. USA 119(32), e2122566119 (2022). https://www.pnas.org/doi/full/10.1073/pnas.2122566119

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