The Aguilar group is focused understanding transcriptional and epigenetic mechanisms of skeletal muscle stem cells in diverse contexts such as regeneration after injury and aging. We focus on this area because there are little to no therapies for skeletal muscle after injury or aging. We use various types of in-vivo and in-vitro models in combination with genomic assays and high-throughput sequencing to study these molecular mechanisms.
Synthetic polymers have been used as a molecular platform to develop host-defense antimicrobial peptide (AMP) mimics toward the development of “polymer antibiotics” which are effective in killing drug-resistant bacteria. Our research has been centered on the AMP-mimetic design and chemical optimization strategies as well as the biological and biophysical implications of AMP mimicry by synthetic polymers. The AMP-mimetic polymers showed broad-spectrum activity, rapid bactericidal activity, and low propensity for resistance development in bacteria, which represent the hallmarks of AMPs. The polymers form amphipathic conformations capable of membrane disruption upon binding to bacterial membrane, which recapitulates the folding of alpha-helical AMPs. We propose a new perception that AMP-mimetic polymers are an inherently bioactive platform as whole molecules, which mimic more than the side chain functionalities of AMPs. The chemical and structural diversity of polymers will expand the possibilities for new antimicrobial materials including macromolecules and molecular assemblies with tailored activity. This type of synthetic polymers is cost-effective, suitable for large-scale production, and tunable for diverse applications, providing great potential for the development of versatile platforms that can be used as direct therapeutics or attached on surfaces.
Lei Chen’s group focus on applying data science tools to advanced manufacturing. Chen’s research expertise and interests are to integrate the physics-based computational and experimental methods and data-driven approaches, to exploit the fundamental phenomena emerged in advanced manufacturing and to establish the design protocol for optimizing the materials and process parameters of as-fabricated parts for quality control. Current research can be summarized by:
1 One of significant challenges in additive manufacturing (AM) is the presence of heterogeneous sources of uncertainty involved in the complex layer-wise processes under non-equilibrium conditions that lead to variability in the microstructure and properties of as-built components. Consequently, it is extremely challenging to repeat the manufacturing of a high-quality product in mass production, and current practice usually reverts to trial-and-error techniques that are very time-consuming and costly. This research aims to develop an uncertainty quantification framework by bringing together physical modeling, machine-learning (ML), and experiments.
2 Computational microstructure optimization of piezocomposites involves iterative searches to achieve the desired combination of properties demanded by a selected application. Traditional analytical-based optimization methods suffer from the searching efficiency and result optimality due to high dimensionality of microstructure space, complicated electrical and mechanical coupling and non-uniqueness of solutions. Moreover, AM process inherently poses several manufacturing constraints e.g., the minimum feature size and the porosity in the piezoelectric ceramics as well as at the ceramics-polymer interface. It is challenging to include such manufacturing constraints since they are not explicitly available. This research aims to develop a novel data-driven framework for microstructure optimization of AM piezoelectric composites by leveraging extensive physics-based simulation data as well as limited amount of measurement data from AM process.
3 Lithium (Li) and other alkali metals (e.g., sodium and potassium) are very attractive electrode candidates for the next-generation rechargeable batteries that promise several times higher energy density at lower cost. However, Li-dendrite formation severely limits the commercialization of Li-metal batteries, either because dendrite pieces lose electrical contact with the rest of the Li-electrode or because growing dendrites can penetrate the separator and lead to short circuits. This research aims to develop a computational model to accelerate the design of dendrite-free Li-metal batteries.
Dr. Lee’s research in data science concerns biological questions in systems biology and network medicine by developing algorithms and models through a combination of statistical/machine learning, information theory, and network theory applied to multi-dimensional large-scale data. His projects have covered genomics, transcriptomics, proteomics, and metabolomics from yeast to mouse to human for integrative analysis of regulatory networks on multiple molecular levels, which also incorporates large-scale public databases such as GO for functional annotation, PDB for molecular structures, and PubChem and LINCS for drugs or small compounds. He previously carried out proteomics and metabolomics along with a computational derivation of dynamic protein complexes for IL-3 activation and cell cycle in murine pro-B cells (Lee et al., Cell Reports 2017), for which he developed integrative analytical tools using diverse approaches from machine learning and network theory. His ongoing interests in methodology include machine/deep learning and topological Kolmogorov-Sinai entropy-based network theory, which are applied to (1) multi-level dynamic regulatory networks in immune response, cell cycle, and cancer metabolism and (2) mass spectrometry-based omics data analysis.
Nils G. Walter, PhD, is the Francis S. Collins Collegiate Professor of Chemistry, Biophysics and Biological Chemistry, College of Literature, Science, and the Arts and Professor of Biological Chemistry, Medical School, at the University of Michigan, Ann Arbor.
Nature and Nanotechnology likewise employ nanoscale machines that self-assemble into structures of complex architecture and functionality. Fluorescence microscopy offers a non-invasive tool to probe and ultimately dissect and control these nanoassemblies in real-time. In particular, single molecule fluorescence resonance energy transfer (smFRET) allows us to measure distances at the 2-8 nm scale, whereas complementary super-resolution localization techniques based on Gaussian fitting of imaged point spread functions (PSFs) measure distances in the 10 nm and longer range. In terms of Big Data Analysis, we have developed a method for the intracellular single molecule, high-resolution localization and counting (iSHiRLoC) of microRNAs (miRNAs), a large group of gene silencers with profound roles in our body, from stem cell development to cancer. Microinjected, singly-fluorophore labeled, functional miRNAs are tracked at super-resolution within individual diffusing particles. Observed mobility and mRNA dependent assembly changes suggest the existence of two kinetically distinct assembly processes. We are currently feeding these data into a single molecule systems biology pipeline to bring into focus the unifying molecular mechanism of such a ubiquitous gene regulatory pathway. In addition, we are using cluster analysis of smFRET time traces to show that large RNA processing machines such as single spliceosomes – responsible for the accurate removal of all intervening sequences (introns) in pre-messenger RNAs – are working as biased Brownian ratchet machines. On the opposite end of the application spectrum, we utilize smFRET and super-resolution fluorescence microscopy to monitor enhanced enzyme cascades and nanorobots engineered to self-assemble and function on DNA origami.
Jerome P. Lynch, PhD, is Professor and Donald Malloure Department Chair of the Civil and Environmental Engineering Department in the College of Engineering in the University of Michigan, Ann Arbor.
Prof. Lynch’s group works at the forefront of deploying large-scale sensor networks to the built environment for monitoring and control of civil infrastructure systems including bridges, roads, rail networks, and pipelines; this research portfolio falls within the broader class of cyber-physical systems (CPS). To maximize the benefit of the massive data sets, they collect from operational infrastructure systems, and undertake research in the area of relational and NoSQL database systems, cloud-based analytics, and data visualization technologies. In addition, their algorithmic work is focused on the use of statistical signal processing, pattern classification, machine learning, and model inversion/updating techniques to automate the interrogation sensor data collected. The ultimate aim of Prof. Lynch’s work is to harness the full potential of data science to provide system users with real-time, actionable information obtained from the raw sensor data collected.