Join us for Symposium closing remarks by Anne Hultgren, PhD, Executive Director of the Arnold and Mabel Beckman Foundation, including a tribute to William H. May, presentation of four appreciation awards for service to the Program Executive Committees, and acknowledgement of trivia and points winners.

Achieving long-term success as a clinician-scientist is one of the biggest challenges for those who choose to pursue an MD-PhD. After 18 years of continuous training after high school, I finally embarked on my first "real job" as a faculty member at the Moran Eye Center of the University of Utah in 1995. In this talk, I will discuss how I have balanced a busy clinical retina practice, an NIH-funded basic research laboratory, and my family life during my 25-year academic medicine career.

During this presentation, I will discuss the career trajectory from ranching a small Eastern Montana family farm and ranch to the study of axonal morphology as a Beckman Scholar. I will delve into the challenges of medical school and choosing a final career path. Chief Flight Physician at University of Chicago Medicine with a husband 1500 miles away was completely feasible. From Chicago, it was back to my Montana roots practicing as a rural Emergency Medicine Physician and first female Partner in an independent physician group. The considerations of academic vs rural medicine, balancing motherhood with your career, breaking through the unforeseen barriers of being a woman in medicine and how it all comes together will be a topic of this discussion. Farmer, Scientist, Physician and Mother...you can do it all.

Academic labs, start-up companies, new business ventures within large businesses:  are they really so different? This presentation will trace my career trajectory from an established full professor at a major research university to the quintessential start-up CEO, and the stops in between. It will highlight some common themes:  a dedicated focus on what is in front of you, the inherent entrepreneurial element within scientific research and development, and the importance of addressing significant problems, with an emphasis on Spear Bio Inc., a NewCo formed to address the significant performance gap in diagnostic tests based on small volume, non-invasive samples.

When you set out on your career journey, you have no idea where it will take you…and that’s part of the fun! But at some point or another, we have all questioned our career choices or waffled on what to do next. Lindsay will share her story of what felt like a disjointed series of steps from undergrad, to grad, to industry research only to look back and realize there was a lovely thread connecting it all together that she couldn’t have planned. Join Lindsay for her talk to learn how following your passion will always put you on the “right” path.

Starting off your career in academia is in some ways like starting a new relationship. Do they like me? What do we have in common? Am I empowered to be my best self? My presentation will focus on my experiences at PUIs (predominately undergraduate institutions) and lessons learned from my years an assistant professor including: 1) How did I find a good match? 2) What did I need from myself and my colleagues to be successful? 3) How did I preserve my independent identity separate from work? These lessons will be presented with anecdotes and presented from the gaze of being a queer Black male in science. I'll conclude with posing a set of key questions to keep in mind as you start your journey.

My experiences as a tenure-track assistant professor at a primarily undergraduate institution will be highlighted, including the expected and unexpected responsibilities of teaching, research, and service. I will touch on my biomedical research and how undergraduates have been able to successfully contribute to the work. Lessons learned and disasters (mostly) averted will be discussed. In addition, I will detail my previous professional experiences and preparation.    

In 11th grade chemistry, Mrs. Dahl’s description of the correlation between the structure of graphite sheets and pencil lead flaking onto the page as I wrote connected the abstract symbols on the page to the real world in a way that changed my perspective forever. It introduced me to the delight that can come when previously obscure ideas not only make sense but illustrate deeper concepts. That experience was the first of many that propelled me to develop spectroscopic and numerical tools for studying molecular interactions and persevere when personal or societal barriers made continuing a challenge. This talk will interweave some of the highlights of my personal journey with a discussion of scientific community’s efforts to increase the participation of women and minorities. The talk also will suggest a shift in focus intended to help young scientists of all backgrounds when they face adversity, and the mentors and leaders who want to support them.

Grab a cup of your favorite coffee or tea and join the Beckman team for a quick hello to kick off the day.

Open to all guests, the Poster Session will feature research poster presentations by Day 2 Presenters in the virtual poster hall. All posters are available for viewing as PDFs, categorized by program and discipline and searchable by name. Real-time 1:1 and group text chat and video chat options enable discussion with the presenter and other guests.

We’ve got breakout rooms set up for discussions about BYI Final Presentations, Cryo-EM, and Light-Sheet Microscopy + Data Science Presentations. Enter the Zoom and move freely between breakout rooms to ask your questions and hear others.

Let’s have some fun with trivia! Join Brian Goess, PhD and Andrea Tartaro, PhD to test your knowledge of all things Beckman. Top scorer wins a prize!

Now that you’ve had time to process the lightning talks during our Beckman Briefings session, you may have additional questions. Meet with the speakers to ask about their research and learn more.

The three-dimensional shape and conformation of small-molecule ligands are critical for biomolecular recognition, yet encoding 3D geometry has not improved ligand-based virtual screening approaches. We describe an end-to-end deep learning approach that operates directly on small-molecule conformational ensembles and identifies key conformational poses of small-molecules. Our networks leverage two levels of representation learning: 1) individual conformers are first encoded as spatial graphs using a graph neural network, and 2) sampled conformational ensembles are represented as sets using an attention mechanism to aggregate over individual instances. We demonstrate the feasibility of this approach on a simple task based on bidentate coordination of biaryl ligands, and show how attention-based pooling can elucidate key conformational poses in tasks based on molecular geometry. This work illustrates how set-based learning approaches may be further developed for small molecule-based virtual screening.

In contrast to crystalline solids, liquids possess no long-range order. Nonetheless, many liquids still display significant amounts of local structure which can strongly influence their properties. I will discuss my efforts to apply reticular chemistry—the use of rigid molecular building blocks with well-defined bonding geometries—to influence the properties of ionic liquids. Specifically, I will describe a strategy to convert a member of a well-known class of hydrogen-bonded organic frameworks (HOFs) into an ionic liquid and will show that many of the structural features present in the HOF are preserved in the liquid state. In the solid state, the guanidinium sulfonate HOFs form an extended layer structure due to hydrogen bonding between the guanidinium and sulfonate groups. Methylation of the guanidinium gives an analogous compound (MeG)2(PEDS) (MeG = methylguanidinum; PEDS = diphenylether disulfonate) which is a viscous ionic liquid above 43 °C and an amorphous glass below. Remarkably, the application of moderate pressures causes this liquid to crystallize as an analog to the original hydrogen-bonded framework structure with incorporation of gas. This process is similar to clathrate hydrate formation, which occurs in water under low temperature and high-pressure conditions. However, both the enthalpy and entropy of formation of the (MeG)2(PEDS) solid phase are unusually small relative to most clathrates, indicating that the ionic liquid phase already possess a significant degree of local structure prior to crystallization. I corroborate this finding with infrared spectroscopy and structural studies of the liquid state.

Asymmetric olefin hydrocyanation generally involves the formal addition of hydrogen cyanide across an alkene, through in situ generation or direct utilization of the highly toxic gaseous form. We have developed a dual CuH/Pd-catalyzed asymmetric cyanide-free olefin hydrocyanation process that relies on an oxazole as a nitrile equivalent. This method allowed for the formal asymmetric Markovnikov hydrocyanation of vinyl arenes and the anti-Markovnikov hydrocyanation of unactivated olefins.

Porous materials such as zeolites and metal-organic frameworks perform a range of useful functions, from heterogeneous catalysis to gas separation. Embedding transition metal active sites in these rigid lattices can turn on modes of reactivity that are not otherwise attainable. This presentation provides a vignette of my work to develop lattice strain as a design principle, enabling activation of strong C-H bonds, as well as cooperative gas adsorption.

In recent years, a new type of synthetic microparticle has captured the imagination of researchers across the physical and biological sciences. These so-called active colloids convert chemical or environmental free energy into irreversible directed motion. Impressively, the active force generated by the particles can lead to self-propelling speeds of tens of hundreds of microns per second. Active colloids challenge our theoretical understanding of nonequilibrium phenomena and simultaneously represent a potentially innovative approach to directed transport and material design at the microscale.  In this talk, I will discuss one of the most striking features of active colloids, which is their rich and complex nonequilibrium phase behavior. Special emphasis will be given to motility-induced phase separation where purely repulsive active colloids undergo a liquid-gas phase transition. This talk will highlight our quantitative understanding of this phenomenon by generalizing concepts in classical statistical mechanics and liquid state theory to active systems. This newfound understanding can be leveraged to improve the self-assembly of many complex colloidal structures using active colloids.

Covalent organic framework (COF) materials are a class of crystalline, permanently porous polymers with a regular reticular architecture. The stable covalent bonds and tunable pore sizes seem to optimally position COFs as functional membranes for energy-efficient separations, with intuitive structure-property relationships. Thick, polycrystalline COF films have been reported to separate dyes, salts, bacteria, and nanoparticles on the basis of size-selective transport through ordered pores. This talk will highlight a paired experimental and computational approach that identified adsorption as the primary mechanism driving molecular separations in these state-of-the-art films, rather than size-selective sieving. Our results suggest that separations based on differential transport through ordered COF pores remain an important yet unrealized frontier. Efforts to improve the routine materials quality of COF films, critical towards the goal of realizing a size-sieving membrane, are ongoing

Selective C–H activation remains one of the most intensely studied reactions across many fields of chemistry, due to its applications in both industrial and fine chemicals synthesis. Although chlorine radicals have been established as potent hydrogen-atom abstraction agents in free-radical chlorination reactions and, more recently, in photoredox catalysis, the high reactivity of these intermediates severely limits their selectivity. We demonstrate that the secondary coordination sphere of a metal complex can confine photoeliminated chlorine radicals and impart steric control over their reactivity. Specifically, a series of pyridinediimine iron(iii) chloride complexes exhibit activity for photochemical alkane C–H functionalization with selectivity for primary and secondary C–H bonds, overriding thermodynamic preference for weaker tertiary C–H bonds. Photocrystallography and time-resolved transient absorption spectroscopy experiments confirm that this site-selective reactivity arises from the generation of an arene–Cl• complex within the steric environment enforced by the iron secondary coordination sphere.

Organic solar cells are ideal for semi-transparent applications due to their “peaky” absorption, which allows them to selectively absorb non-visible photons while transmitting visible light. This talk will focus on the development of a novel series of photovoltaic donor molecules that selectively absorb UV-light, and the integration of these molecules into high-performance transparent solar cells. We find that by modifying the absorption cutoff wavelength of the materials through chemical synthesis, we can tune both the power generation capability of the solar cells, as well as their aesthetic properties like color neutrality and transparency.

Light is a ubiquitous and critical resource in our daily lives. Light facilitates our ability to see, enables near-instantaneous global communications, and is the sole energy source for the photosynthetic organisms that comprise the base of the food chain on Earth. Around the world, scientists and engineers are pushing the limits of light to create the next generation of optical technologies that will enable ultrafast optical computers, self-driving cars, rapid medical diagnostics, and address the global climate crisis. In this presentation, I will introduce optically coupled electron microscopy, which couples light into, and collects light out of, a standard transmission electron microscope. This technique allows us to image the structural dynamics of materials under illumination with the atomic-resolution afforded by an electron microscope The studies highlighted in this presentation will span sustainability and medicine and are likely just the tip of the iceberg in what is possible when studying optical materials in the TEM.

We’ve got breakout rooms set up for discussions about our on-demand Bio-Chem Presentations. Enter the Zoom and move freely between breakout rooms to ask your questions and hear others.

Calling all BYI, Postdoc, BSP and Legacy Mentors! Connect with your fellow Mentors starting with around-the-Zoom introductions followed by open discussion. Ask your questions, share tips and trends, and collaborate on challenges.

The human mind is one of the most breathtakingly complex and still poorly understood things in nature. And yet, the mind is the tool with which we attempt to understand our world, ourselves, and it. The mind is in fact the most essential tool in any scientist or researcher’s employ. I have used mine to pour over countless scientific questions throughout my career: from molecules to populations, and from NMR spectroscopy to single cell expression patterns. All the tools that we use to conduct experiments, collect data, and analyze our results would be useless and merely collecting dust if we did not have our minds’ curiosity, logic, ingenuity, and acuity to formulate the experiments, troubleshoot problems, and craft the stories that weave together discrete findings into compelling stories to explain life, the universe and everything. 

So what happens when you have all the tools, a lab to conduct your research, scientific support, and excellent advisement, but your most important tool, your mind, betrays you? Science cannot be pursued without a sound mind, yet confoundingly, scientific researchers have a long history of neglecting and abusing their greatest tool. This has led to a global epidemic of poor mental health among academics with upwards of 6-8 times the rate of depression and anxiety among postgraduates than the general population. The mind is dependent on the brain, and like any other organ we possess, it can and does wear out, malfunction, and even break. Like most diseases, mental illnesses are due to a confluence of biological and environmental factors. Yet our community often fails to recognize this and instead stigmatizes these natural and expected aspects of brain biology resulting in fear, avoidance, and failure to address these issues in practical ways. My research and my academic life have led me on a tortuous path to try to make sense out of our most important tool and encourage all researchers to value it: our minds.

This talk is a deeply personal reflection on coping with issues surrounding mental health as a student in STEM, particularly as a PhD student in a research lab. I identify several sources of anxiety and depression which are often felt by students in research laboratories, whether or not the principal investigator is actively promoting a toxic work environment. I then discuss my own struggles with anxiety, which manifested in many physiological forms, some of which required intervention.

Grab a cup of your favorite coffee or tea and join the Beckman team for a quick hello to start your day.

Open to all guests, the Poster Session will feature research poster presentations by Day 1 Presenters in the virtual poster hall. All posters are available for viewing as PDFs, categorized by program and discipline and searchable by name. Real-time 1:1 and group text chat and video chat options enable discussion with the presenter and other guests.

With highly competitive NIH budgets and ever-increasing restrictions on federal spending, getting noticed and winning an NIH R grant is far more difficult and highly competitive than it has ever been. To be competitive today, new and inexperienced grant writers must learn the essentials of strong grantsmanship that is rarely taught today in academia. In 2019, the overall success rate for NIH R01 grants was just 20%, with some Institutes approving only 10% of submitted applications. This means that NIH-wide, nearly 8 out of 10 R01 application submissions are rejected. If you want to be one of the PIs that receives research grant funding, you must be able to write your grant so that it prevails over the five review criteria which generates your overall impact score. Many investigators, especially new investigators, don’t know how to write a winning grant or understand what pitfalls to avoid. Writing a winning grant proposal that gets noticed by reviewers requires that investigators produce a highly polished, cohesive grant that really knocks it out of the park for its significance, innovation, and approach while showing that it will have a major impact on their field. In this webinar, Dr. Dant will provide you with details of what reviewers want and don’t want to see in your R01 grant proposal. Ultimately, you’ll learn how to write your next R01 grant in a way that will get reviewer’s attention and influence them to approve and fund your research proposal.

As part of the “How to Get the Right Postdoc Position” Mentoring Series, I will share a reflective look at my career journey, including finding and deciding on my postdoc experience and then my faculty position. A postdoc experience can be a great opportunity to support your mentoring and career development though networking and fellowships. I will also present general advice about why mentorship matters, what to look for when you pick a mentor, and how to make sure that you go beyond finding a single good mentor to create a mentoring team!

Kent will briefly discuss some of his current activities, research and otherwise, associated with being a professor and research principal investigator. He will then present background and history related to the path that he has taken in his professional career, focusing on some of the key decision points and rationales for going the direction he chose. We will emphasize the PhD to postdoc transition, and provide opportunities for questions and open discussion where possible.

My goal for this presentation is to provide guidance for both mentor and mentee resulting in an evidence-based resume or CV. The ‘how to’ session will be specific to those wanting to pursue a graduate degree. The step-by-step tips will draw from my experiences as an academic mentor and from my committee work at the institutional, regional, and national level.

The vast majority of graduate students seek their advanced degree as a basis for seeking a job, whether that be in industry, a government lab, or one of many types of research and teaching gigs found in higher education. None of these are volunteer positions, so naturally, a successful job search is defined by an employer agreeing to provide you with financial compensation for your future services. The more that you understand the employment you seek, the clearer the path to that endpoint. Even in this situation, how do you introduce yourself and explain your skill set, in a timely and effective manner? How do you approach a process that appears linear and static, but has a career-defining temporal component? We'll begin with the classics: crafting a resume and research summary.

Mastering the art of abstract writing is essential to your research career. Throughout your academic career, you will write a large number of abstracts, covering different projects and aimed at a wide range of audiences.

Grab a cup of your favorite coffee or tea and join the Beckman team for around-the-Zoom introductions – a casual icebreaker to kick-off Symposium and get to know your fellow attendees.

Chosen due to its structural similarity with previously characterized chiral tagging candidates, trans-2-fluoro-3-(trifluoromethyl)oxirane (tFTFO) is a small chiral molecule to be investigated, both theoretically and experimentally, as a potential chiral tagging molecule. With a strong, simple rotational spectrum, tFTFO shows promise for applications in chiral analysis through the conversion of enantiomers into spectroscopically distinct diastereomeric species through noncovalent attachment. Second order Møller-Plesset (MP2) perturbation theory is used to optimize the structure of tFTFO and of its heterodimer with the argon atom, generating rotational constants to guide spectral analysis. The rotational spectrum of tFTFO and of Ar-tFTFO is obtained using Fourier transform microwave spectroscopy from 5.6 to 18.1 GHz. The spectrum is analyzed to determine the rotational constants and many centrifugal distortion constants for the most abundant species and the significantly abundant singly substituted isotopologues of tFTFO and Ar-tFTFO. The rotational constants for both the monomer and the argon complex are then utilized to find the experimental equilibrium and zero-point average structures via Kraitchman analysis and a structure fitting program, respectively. This work shows that the structure of the argon complex is distinct from the structures previously described for the 3,3,3-trifluoro-, 3,3-difluoro-, and 3-fluoro-1,2-epoxypropane species, suggesting that the addition of the lone fluorine atom alters bonding in the epoxy moiety. tFTFO's dimer with a chiral anlyte is also studied to assess its effectiveness as a chiral tag. 

Dynamically activated differential adhesion between cell subpopulations drives multicellular tissue patterning in development and disease. Previous studies have explored this process in heterogeneous spheroids by using synthetically engineered systems, in which initially non-adherent cells engage in bi-directional signaling to activate differential cadherin expression. While synthetic systems provide an excellent in vitro model to observe pattern formation, computational techniques can be leveraged to systematically explore the key parameters that drive the emergence of different patterns. We developed and validated two- and three-dimensional computational agent-based models (ABMs) of cell patterning in spheroids and demonstrated how varying the initial cell seeding ratio, signaling sensitivity, and homotypic adhesion strengths between cells lead to unique spheroid patterns. We developed novel model exploration techniques that use machine learning to identify how combinations of cell-to-cell signaling parameters in this system drive the formation of specific multicell patterns. We also deployed the model in reverse as a tool to design new synthetic cell signaling circuits based on a desired final multicell pattern. 

The fidelity of intracellular signaling pathways requires that cells control the production of signaling agents in space and in time. Phosphatidic acid (PA) is both a central phospholipid biosynthetic intermediate and a multifunctional lipid second messenger produced at several discrete subcellular locations. The modes of action of PA differ based on upstream stimulus, biosynthetic source, and site of production. How cells regulate the local production of PA to direct diverse signaling outcomes remains elusive. To unravel these questions, we have significantly expanded the toolkit for visualizing and perturbing cellular PA production. These approaches have revealed new functions of spatiotemporally defined pools of PA in response to physiological and pathological stimuli. Our work highlights the power of combining bioorthogonal chemistries, chemoenzymatic tagging, directed evolution, and optogenetics to shed light on cell signaling pathways.

Macrophages and T helper 17 (Th17) cells, an important subset of CD4+ T cells, help to eliminate infectious pathogens that have invaded our tissues. Despite the critical roles of these cells in immunity, how the immune system regulates the production and maintenance of both cell types remains poorly understood. Here, we report a synthetic immunology approach using a photoactivatable immune modulator (PIM) to control the activities of these cells on demand with spatial and temporal precision to help elucidate their dynamic roles during the host immune response. In this chemical strategy, we developed a latent inhibitor/agonist that upon photochemical activation releases a small-molecule inhibitor or ligand that can inactivate or activate the respective cell type. We envision that this chemical approach will enable an understanding of the dynamic functions and behaviors of these immune cells in vivo during immune responses and in mouse models of inflammatory disease.

Secondary organic aerosols (SOA) have significant impact on climate, air quality, and human health. Thus, it is critical to study the chemical fate of SOA particles, which is driven in part by photochemistry. Oxaloacetic acid (OAA) constitutes a broader class of keto-carboxylic acids commonly observed in the atmospheric environment. Our experiments showed that OAA undergoes both decarboxylation reaction and photodissociation. UV-Vis spectroscopy was used to capture the time decay of characteristic π*←n carbonyl band of OAA in aqueous solution mimicking conditions in cloud droplets. Vapor pressure of OAA is too low to study in the gaseous phase, therefore, more volatile diethyl oxaloacetate, was used to examine gas phase photochemistry associated with the carbonyl group of OAA. Photochemical processes involving OAA may unfold on picosecond time scales, making photochemical dynamics extremely hard to observe in experiments. Therefore, theoretical method simulating the excited state is of central importance to photochemistry in organic aerosol formations. Nonadiabatic radiationless transitions between-electron states are notoriously hard to control and proceed through “dark”, experimentally elusive conical intersections (CIs). For ground state, the Born-Oppenheimer (BO) approximation, which separates the electronic and nuclear degrees of freedom, is generally accurate. However, the BO approximation breaks down for excited states where two or more BO potential energy surface (PES) are strongly coupled. To capture the excited states more accurately, nonadiabatic molecular dynamics (NAMD) is employed, which demonstrates more efficient sampling of nonadiabatic processes accounting for nuclear quantum effects. The use of both experiments and NAMD simulations will make it possible to establish the atomistic mechanism of the photochemical processes, unveil ultrafast reaction pathways and dynamics, and determine observables such as yields and long-lived intermediates.

As chemists, we are familiar with guidelines and heuristics that help us to predict how chemical reactions will proceed. My group is interested to expand these heuristics to understand if we can predict topological materials, which is a class of quantum matter. In this talk, I will show how delocalized chemical bonds in certain structural networks allow us to define chemical descriptors that predict band inversions. Using these descriptors, we found a layered, antiferromagnetic van der Waals material with very high mobility. This is the first time that these properties are combined in one material, which is promising for applications in novel types of data storage or computing devices. We further implemented our heuristics to discover novel complex topological phases, including magnetic ones, and phases that are in competition with complex structural distortions. I will show how structural distortions can have a positive effect on topological band structures. 

Color centers in diamond have emerged as a leading platform in the field of "quantum sensing", broadly defined as the use of qubit systems to measure environmental parameters. I will discuss ongoing work in my lab to develop new spectroscopic and imaging tools based on diamond quantum sensors. I will focus on recent milestones towards performing NMR spectroscopy at the scale of single cells, including the demonstration of multidimensional NMR spectroscopy in a microfluidic chip. I will also highlight efforts to improve the spectral resolution and sensitivity for the ultimate goal of identifying and quantifying metabolites under physiological conditions.

Biological investigations at the cellular and molecular level offer exciting opportunities for diagnosis and monitoring of a disease, as well as for gaining biological insights to develop effective therapies. Well matched in size, microfluidic devices are ideally suited for probing cells as they offer unique capabilities to deterministically manipulate cells with high precision under a variety of forces. As such, any contrast in biophysical and biochemical properties among cells can be used to effectively separate different subpopulations. To utilize these extensive manipulation capabilities in performing quantitative measurements of different cell properties, we developed a sensor technology that allows electronic monitoring of cell manipulation within a microfluidic device. In my talk, I will present assays, in which cells are spatiotemporally segregated based on differences in their properties as built-in electrical sensors digitally record the trajectory of each and every cell in a microfluidic device to perform high-throughput physical and chemical analysis of cell populations.

The ability of molecules to pack into ordered, crystalline assemblies, provided the right conditions, has been exploited for decades to explore their atomic structure. Still, many molecules fail to form ordered crystals of sufficient size for conventional structure determination, and the molecular causes for this are still poorly understood. Electron diffraction has shown promise in this direction, opening up the possibility of elucidating structures from crystals only a few hundred nanometers thick. This ability is changing the way crystallography is performed for both small and large molecules.

Ae. aegypti mosquitoes are vectors for pathogens that cause Zika, dengue fever, and chikungunya. A single mating event provides a female with sperm to fertilize all of the offspring she will produce for the rest of her life. During mating, male mosquitoes transfer peptide signals that act on receptors expressed in the female that block her from mating with other males. This enforces his paternity and ensures that he is the father of all of her offspring. These signals can also be used in a form of competition between two species termed “satyrization” when males of one species inappropriately “mate” with females of another species and block females from mating with males of their own species. This prevents the females from successfully reproducing, effectively sterilizing them. We aim to identify peptides transferred from the male to the female, determine which receptors they activate in the female, and ask how interspecies competition may affect these receptors. The molecules that we discover could be used to develop new ways to control mosquito populations by blocking female reproduction.

Biological systems are highly complex due to the intricate spatial organizations of different types of cells and the heterogeneous nature of living cells. Characterizing the phenotypic behavior of single cells within their native microenvironment is crucial in revealing the pathophysiology of tissue. Current tools for studying multicellular systems are often limited to destructive biochemical analysis, characterization of dissociated cells or molecule-specific imaging with fluorescent labels. These limitations prohibit assessment of key phenotypic properties such as cell size and growth, metabolic status, microenvironmental change, and cell interactions. We developed a multimodal multiphoton optical imaging system to address this challenge. It incorporates two-photon fluorescence, transient absorption microscopy, and stimulated Raman scattering microscopy on the same platform, which enables comprehensive imaging of cell shape, size, density, growth, metabolism, type, and interaction. The platform is applicable to not only cell cultures in 2D and 3D, but also living animals. We aim to employ this platform to study a wide range of biological questions including tumor development, drug transport, and neuro-vascular coupling.

Despite the structural diversity enabled by modern advances in polymer synthesis, greater than 60% of world plastic production remains dominated by polyolefins. These high-volume, low-cost engineering thermoplastics are made from a small sub-set of petroleum derived monomers and demonstrate diverse thermomechanical properties, attractive chemical resistance, and excellent processability. Creating sustainable materials that compete with the performance and value proposition of polyolefins is a grand challenge for the field of polymer science. The goal of research in the Leibfarth group is to develop synthetic methods that transform readily available starting materials into functional and sustainable thermoplastics with molecular-level precision. This goal informs our approach that seeks to develop stereoselective polymerization methods that engender emergent polymer properties from simple chemical building blocks. These concepts have resulted in platform synthetic methods that enhance the thermomechanical, adhesion, and transport properties of next-generation thermoplastics while also uncovering mechanistic insights that broadly inform synthetic method development.

Metal-organic frameworks (MOFs) hold promise across a wide range of applications, including gas storage and separations, delivery of therapeutic agents, catalysis, and sensing. MOF crystal phase, morphology, and surface chemistry, all results of the crystallization process, dictate the bulk properties of the MOF such as active surface area, separation efficiency, and overall performance. Indeed, rationally designed MOF crystals have the potential to allow substantial energy savings in industrial separations and to open up new opportunities in catalysis. Despite this potential, there is currently little understanding of the synthetic principles behind MOF crystallization, and the synthesis of MOF crystals of a given phase or morphology typically relies on brute-force strategies, including trial-and-error and high-throughput screening rather than rational design. In this talk, I will discuss new methods for rationally controlling the size and shape of anisotropic MOF crystals.

Transient receptor potential vanilloid 2 (TRPV2) plays a critical role in a variety of physiological and pathophysiological processes, putting TRPV2 on the list of important drug targets. Yet, specific TRPV2 agonists and antagonists are currently unavailable. Their development requires a precise knowledge of how the currently known non-specific small molecules interact with TRPV2 at the molecular level. Here we present TRPV2 structures in ligand-bound states resolved by cryo-electron microscopy in the presence of 2-aminoethoxydiphenyl borate (2-ABP), 2-APB with doxorubicin (DOXO), and ruthenium red (RR). We identified a novel 2-APB drug binding site between the S5 helix and S4-S5 linker on two adjacent TRPV2 monomers and determined the mechanism of TRPV2 pore block by RR. We also showed that a large organic molecule like DOXO can enter the TRPV2 pore in the presence of 2-APB. Additionally, we discovered a structural lipid bound in a unique position in the “vanilloid pocket”, which is absent in the 2-APB-bound state of the channel, allowing us to propose a model for TRPV2 channel gating. Together, this work provides a further understanding of TRPV2 function and a structural framework for the development of TRPV2-specific modulators.

Acinetobacter baumannii is a human bacterial pathogen with pronounced morbidity and mortality rates in immunocompromised patients. With the prominent rise of multidrug-resistant strains, understanding the mechanisms by which this bacterium regulates its virulence is imperative for the development of alternative treatments and prevention. Our laboratory has previously showed that one such environmental signal to which A. baumannii responds is light.

     Earlier, we had determined that the photoreceptor BlsA is primarily responsible for light-mediated regulation at 24ºC; BlsA regulates a myriad of virulence factors including iron-uptake, motility, and acetoin metabolism. Through the Beckman funds, we were able to broaden BlsA’s sphere of influence to include A. baumannii’s response to oxidative stress, specifically through differential regulation of catalase and superoxide dismutase activities. Additionally, we showed that specific amino acid residues of the C-terminal region of BlsA are critical for this regulation and interaction with protein partners that effect light-mediated regulatory responses. Ultimately, these findings further characterized the overall structural mechanisms of BlsA that allow light-mediated regulation in A. baumannii at 24ºC, a temperature that reflects the nosocomial environment.

     Notably, we have also found that light regulation occurs at the human-host relevant temperature of 37ºC, a condition at which BlsA no longer functions as an active photoreceptor. In particular, we have shown upregulation of the conjugation of a plasmid conferring multidrug-resistance under darkness. This finding has led us to further clarify the importance of this plasmid for A. baumannii virulence, with primary focus on peroxide resistance, motility, and macrophage uptake of bacteria. 

     Overall, our findings provide a more global insight into how A. baumannii is able to use light as a signal to confer virulence both in and outside of the host.
 

The past decade has witnessed remarkable advances applying the transformative insight of ultrafast spectroscopies to the nanoscale. By coupling femtosecond laser pulses into far-field microscopes, the spatial and energetic evolution of electrons can be correlated to specific micro- and nanoscale structural features, providing important insight into how anisotropic crystal structures, strongly interacting excited states, and structural and electronic defects influence the behavior of active (opto)electronic devices. In this talk, I’ll discuss work done by our group developing and applying ultrafast microscopies that provide new contrast agents and means to correlate structure with function in a variety of nanoscale and bulk materials. I’ll show our efforts developing excited state stimulated Raman microscopy, which provides a means to directly probe how electrons couple with vibrational degrees of freedom on the femtosecond time scale and on sub-200 nm length scales. In addition, I’ll describe recent efforts that have directly correlated electron motion to local crystal structure, thereby directly probing how electron motion is governed by the local defect density and lattice strain in bulk materials.

Schistosomes are parasitic flatworms causing one of the most prevalent infectious diseases from which millions of people are currently suffering. These parasites have very high fecundity and their eggs are both the transmissible agents and the cause of the infection-associated pathology. Given its biomedical significance, the schistosome germline has been a research focus for more than a century. Nonetheless, little is known about the molecular mechanisms that regulate its development. In this talk, I will present our recent progress using single-cell resolved functional genomic analysis to identify the cellular origin of the schistosome germline. We found that, unlike most animals that segregate their germline from soma during embryonic development, schistosomes specify their germ cells from a somatic cell lineage at the onset of juvenile development. In addition, we identify a genetic program that balances proliferation and differentiation of the schistosome germline stem cells. Through single-cell transcriptomic and functional comparisons, we also showed that this germline-specific regulatory program is conserved in the planarian, schistosome's free-living evolutionary cousin, but its function has changed significantly during evolution.