Our People

Ludmilla Aristilde

Unraveling Mechanisms in Environmental Organic Processes and Environmental Biotechnology

The objective of our research activities is to obtain a mechanistic understanding of the “why” and “how” of the environmental behavior of biologically-active organic molecules with implications for environmental contamination, soil fertility, agricultural productivity, and ecosystem health. We are particularly interested in the fate and effects of organic contaminants including herbicides, antibiotics and natural toxins and in the reactivity and fate of important organic substrates and macromolecules in environmental matrices. Our investigative approaches employ a combination of experimental and computational techniques to resolve the mechanisms of the chemical and biochemical interactions relevant to the environmental chemistry and toxicology of these molecules. The long-term goal of our research is to achieve a mechanism-based quantitative evaluation of the potential implications of these bioactive molecules for environmental fate and exposure, chemical transformation, biotechnology, ecosystem health, and carbon dynamics in aquatic and terrestrial environments.

Linda Broadbelt

Exploration of Novel Biochemical Pathways and Bioprivileged Molecules through the Confluence of Kinetic Modeling and Data Science

The scientific motivation driving the work in my research group is unraveling complexity in reacting systems.  We recognize that macroscopic observations are linked to microscopic phenomena, and analysis spanning these regimes provides the best opportunity for fundamental understanding and development of novel engineering strategies.  We are focused on unraveling, understanding, and leveraging complex reaction network in metabolic systems.  Specifically, enzyme promiscuity is capable of opening up vast possibilities for bioproduction of valuable chemicals, where novel biosynthetic pathways can be constructed based on these promiscuous activities. We use automated network generation based on a software platform we have developed jointly with Keith Tyo, called Pickaxe, to develop novel routes to known and novel molecules.  We have generated a set of generalized enzymatic reaction rules that are capable of describing the vast array of known enzymatic transformations, which can be applied in our cheminformatics-based platform, Pickaxe, to predict the entire space of possible metabolic reactions.  We also connect our efforts in synthetic biology to our group’s expertise in homogeneous and heterogenous catalysis, enabling us to create novel hybrid pathways that interface biological and chemocatalysis.

Jaehyuk Choi

The goal of our lab is to elucidate T cell circuitry, identify disease relevant molecular mechanisms, and develop clinically relevant biomarkers and therapeutics

We employ cutting-edge genomics approaches to elucidate the role of T cells in immunohomeostasis and disease. We apply this knowledge to elucidate the cellular players and molecular circuitry that drive pathological changes in the skin in diseases such as skin cancer, cancer of skin immune cells, and autoimmune disease. Currently, there is an unprecedented opportunity to study and modify T cells in the setting of disease. The goal is to translate these findings to clinical trials. Current projects include:

• T cell circuitry: We are combining traditional genetics with functional genomics to elucidate cellular circuitry in tissues and molecular circuitry within cells. These studies reveal novel tissue resident T cells and novel genes that modulate T cell fate, signaling and transcriptional programs.
• Disease-Relevant Molecular Mechanisms: We are using human and animal models to determine how T cells contribute to disease pathogenesis. Currently, the primary foci are cancer and autoimmune or autoinflammatory diseases.
• Clinical Translation: We are actively studying methods to translate our findings into clinically useful biomarkers and novel therapeutics.

Monica Olvera de la Cruz

We are developing models to describe the self-assembly of heterogeneous molecules for synthetic biology applications

Research in the Olvera de la Cruz group is centered around the development of models to describe the self-assembly of heterogeneous molecules including amphiphiles, copolymers and synthetic and biological polyelectrolytes, as well as the segregation and interface adsorption in multicomponent complex fluids. Work by the group has resulted in a revised model of ionic-driven assembly: demonstrating the electrostatic spontaneous symmetry breaking of ionic fibers and membranes, and identifying its relevance to biological functions and to the design of functional materials. The groups investigations into soft and condensed matter physics have advanced scientific knowledge and opened new research fields of technological importance; including gel electrophoreses dynamics, self-organization of molecular electrolytes into bio-mimetic materials, self-assembly of heterogeneous molecules into complex nano-structures, interface adsorption and phase segregation dynamics and structure of multicomponent fluids.

Yogesh Goyal

We are a curiosity-driven laboratory working on a range of problems in single-cell systems biology

Individual cells within genetically homogenous populations can respond differently to inductive signals or cues and adopt distinct fates. We combine novel experimental, computational, and theoretical frameworks to monitor, perturb, model, and ultimately control single-cell variabilities and emergent fate choices in development and disease, including cancer and developmental disorders. We are doing this in three key areas:

• Tracing cellular plasticity and emergent drug resistant fates in single cancer cells
• Mathematical models of heritable transcriptional fluctuations underlying cellular memories
• Engineering plasticity and fate decisions in ex vivo models of development

Neha Kamat

Integrating synthetic biology and biomaterials for fundamental and applied studies with biological membranes

Biological membranes, composed largely of lipids and proteins, define the boundary of our smallest unit of life, the cell. These structures mediate some of the most critical cellular functions, enabling the movement of physical and chemical information, and undergoing complex shape changes to facilitate movement, growth, and division. Research in the Kamat lab aims to understand and harness biological membranes as a biomaterial for fundamental biological studies and engineering applications in diagnostics and disease.

Specifically, we pursue two research thrusts:

1. We assemble model membranes with varying physical properties and measure the impact of these properties on membrane protein folding and function.
2. We engineer membrane-based devices for therapeutic and sensing applications.

Our unique approach to pursuing these goals is to first move outside the cell and build membranes in the laboratory. Using cell-free protein expression systems, we recreate the process of membrane protein synthesis, folding, and membrane integration and measure the effect of membrane biophysical properties on these latter processes. The fundamental biophysical studies we conduct provide mechanistic insights that we use to design membrane-based materials with cell-like capabilities. In turn, the materials we design provide new tools to investigate cellular systems. To accomplish this work, we also use non-natural amphiphiles, such as diblock copolymers, and develop new optical tools for membrane characterization. Our approach of using techniques from synthetic biology and membrane biophysics allows us to measure and change membrane properties, in synthetic and living systems, in new ways.

Ashty Karim

We are enabling carbon-optimized cell-free bioconversions for the industrial production of bioproducts

Industrial biotechnology is one of the most attractive approaches to address the need for low-cost fuels and products from sustainable resources,1,2 and nearly all current investments in biomanufacturing (almost $4B in 2018) are based on production using cells. Unfortunately, the use of cells to produce molecules remains costly, risky, and slow. This is because cells themselves impose inherent limitations on the effective synthesis of bioproducts. One key limitation is that cellular survival objectives are often diametrically opposed to the objectives of biochemical engineers. Another limitation is that cells are carbon positive (they release CO2) and are poor at using potentially profitable and sustainable feedstocks. This dilemma is what has motivated me to develop expertise in cell-free metabolic systems which avoid these constraints.

The core idea of cell-free technologies is that we can conduct precise, complex biomolecular transformations in cell lysates. In other words, cellular machinery harvested from cells that are broken open can be used to manufacture products. Compared to cells, cell-free systems: (i) require less development time to go from concept to production, (ii) provide higher production rates, (iii) do not require the removal of products from cells, and (iv) are tolerant to high levels of toxic molecules. Recognizing these advantages, a few pioneering companies have pursued commercializing cell-free biomanufacturing systems specifically for producing proteins. However, production of non-protein products at anything other than lab-scale demonstrations has not been pursued. Expanding the scope of cell-free biomanufacturing practice would enable production of molecules at a complexity and scale that are orders of magnitude beyond what is feasible today, establishing a range of innovative technologies to transform commercial applications and society.

My research group is developing the engineering design rules for expanding the scope of cell-free biomanufacturing and exploring strategies for carbon-optimized cell-free bioconversion. My group employs analytical approaches to investigate how physiochemical properties lead to biological function in cell-free systems.

Neil Kelleher

The Kelleher Group pioneers cutting-edge technologies for understanding the role of proteins in health and disease and design-build-test cycles for creating synthetic protein-based drugs and diagnostics.

Analysis of whole protein molecules provides the ability to examine protein sequences, mutations, and modifications in unprecedented detail. Proteoforms, or all of the different molecular forms in which a protein can be found, capture all sources of protein variability (i.e., isoforms, SNPs, post-translational modifications, etc.), and thus provide crucial insights into biological function by connecting primary sequence and post-translational modifications. After a breakthrough Nature paper in 2011, Kelleher has continued to push the boundaries of proteomics, most recently culminating in a publication in Science (2022, 375: 411-418). Perspectives published by Kelleher and a consortium of like-minded researchers over the last decade articulating the value of proteoforms and a landmark project to map all proteoforms in the human body (Sci. Adv. 2021, 7: eabk0734) typify their thought leadership in a field seeing a new crescendo of interest and activity in the 2020s.

This ‘top-down’ approach to proteomics has propelled rapid development of new instrumentation and technologies for ultra-high performance mass spectrometry and uncovered new insights on clinically relevant protein targets such as KRAS (Ntai et al., PNAS, 2018) and ApoA-1 (Seckler et al., J Proteome Res., 2018).

‘Native’ top-down proteomics allows faithful preservation of post-translational modifications and non-covalent interactions in protein complexes and bioassemblies. This approach enables characterization of large virus-like capsids and their payloads (Kafader et al., Nature Methods, 2020) and endogenous and synthetic nucleosomes (Schachner et al., Nature Methods, 2021).

Shana Kelley

We are developing new analytical platforms and involve aspects of diverse disciplines ranging from materials chemistry to chemical biology and nanotechnology

Biomolecular Sensors

Our aim is to generate detection systems applicable to the diagnosis and management of a variety of disease states, ideally through the development of wearable and implantable sensors for continuous in vivo monitoring.

Rare/Single Cell Analysis

Our work focuses on the development and application of new technology platforms that allow single cell level information to be collected on billions of cells with a high level of throughput. We have applied our approaches to cell profiling to the development of assays for liquid biopsy, disease screening, cell therapy development and therapeutic target discovery.

Intracellular Molecular Delivery

Delivering molecules into cells can be made more precise with vectors that direct intracellular cargo to particular compartments. Our work has focused on mitochondrial targeting with a versatile peptide based vector that promotes efficient cellular uptake and strong mitochondrial localization.

Sam Kriegman

To bring AI out of the digital realm of bits and pixels and into the real world as robots of diverse size, shape, material, and niche

Sam Kriegman is an assistant professor of computer science, chemical and biological engineering, and mechanical engineering at Northwestern University. He received his PhD in 2020 from the University of Vermont, followed by a postdoc at Tufts University and Harvard University. His research seeks general theories of life, in which the details of carbon-based organisms would represent a special case. As we have yet to invent a time machine or the means of interstellar travel, Sam and his students design, build and breed robotic lifeforms to catch a glimpse of life as it may have arisen here on Earth or as it might exist elsewhere in the universe. An AI2050 Fellow, ISAL Distinguished Early-Career Investigator, and Cozzarelli Prize recipient, his creation of the world’s first AI-designed organisms (the “xenobots”) triggered considerable global media attention and a tidal wave of public discourse, still ongoing, among scientists in several fields, science communicators, and the public.

Joshua Leonard

The Leonard Lab is committed to enabling an emerging paradigm of design-driven medicine by integrating synthetic biology with systems biology to address pressing challenges in medicine and biotechnology

We leverage and pioneer approaches spanning synthetic biology, protein engineering, experimental systems biology, and computational biology to develop technologies such as cell-based “devices” that serve as programmable immune therapies for cancer, novel biomolecular therapies based upon nanoscale vesicles, and engineered biosensors for applications in metabolic engineering and global health. Our long-term areas of interest include:

• Engineering programmable mammalian cell-based therapies
• Enabling design-driven engineering of living systems
• Understanding immune function and immunotherapies through systems biology
• Harnessing extracellular vesicles as therapeutic delivery vehicles

Julius Lucks

Uncovering the principles of molecular design for biology, medicine and biotechnology

Our research seeks to reveal the principles that enable biological systems to sense and adapt to changing environments and to understand how we can use these principles to engineer synthetic biological systems that benefit humankind. A focal point of our work is RNA –a fundamental component of all living systems that enacts genetic, regulatory and catalytic functions by folding into intricate shapes within cells. An overarching approach of our work is to distill the complexity of natural biological systems into design principles that can then be used to build synthetic systems. This dual discovery/synthesis approach allows us to interrogate molecular systems in powerful ways, with each approach informing the other in a cycle of increasing understanding.

Using this approach, we focus on four main research areas:

1. Enabling high-throughput RNA structural biology. We develop tools like SHAPE-Seq that combine chemical probing and next generation sequencing to characterize the structures of hundreds to thousands of RNAs in a single experiment. This data fuels new computational approaches to predict and design RNA structures to understand their biology and engineer their behavior.
2. Discovering new principles of dynamic RNA folding and function. We combine our high throughput structure probing with synthetic biology design approaches and directed evolution to understand how RNA molecules dynamically change their folding and function in biological systems.
3. Impacting human and environmental health with synthetic biotechnologies. We use the fundamental knowledge learned to design RNA biotechnologies that can be used by individuals to monitor the health of themselves and their environments, including the ROSALIND platform for water quality monitoring. We are actively exploring how we can merge these approaches with materials science to extend the capability of our diagnostic systems.
4. Interfacing synthetic biology with social science. Recently we have begun to collaborate with social scientists, policy researchers and law experts to study how users interact with our technologies, and how they can be tailored to benefit their lives.

Niall Mangan

Data-driven mechanistic modeling for complex systems design

Niall Mangan is an assistant professor of engineering sciences and applied mathematics at Northwestern University. Niall received a dual B.S. in mathematics and physics from Clarkson University in Potsdam, NY, and her Ph.D. in systems biology from Harvard University in Cambridge, MA. Starting in 2013, she was a postdoctoral associate in the Buonassisi Photovoltaics Lab at the Massachusetts Institute of Technology in Cambridge, MA. In 2016, she became an acting assistant professor in applied mathematics at the University of Washington in Seattle, WA, and a summer research associate with the Institute for Disease Modeling in Bellevue, WA. In 2018, Niall started her research group at Northwestern.

Her group focuses on biological and physical modeling and data-driven methods for model identification, parameter fitting, and systems design. The group works closely with experimental collaborators to develop models for complex systems such as metabolic and regulatory systems, further understand how different mechanisms interact, and provide engineering design rules. Niall has long been interested in alternative energy development and sustainability, including harnessing photosynthesis and CO2 fixation in cyanobacteria, Chlamydomonas, and plants. Key questions include how spatial organization and temporal organization of metabolism can be used to enhance biochemical production. The group’s mathematical methods development sits at the intersection of dynamical systems, statistics, optimization, and physical modeling. By developing data-driven methods to discover mechanistic models, her group seeks to accelerate the design, build, test, and learn cycle, particularly in high-throughput experiments in cell-free systems.

Milan Mrksich

We aim to develop breakthrough therapeutics, diagnostics, and materials by engineering complex, protein-based molecules we call Megamolecules

Our group uses the tools of synthetic biology, organic chemistry, and engineering to address important challenges in and at the intersection of chemistry and biology.

Our group pioneered a new platform for engineering protein-based molecules – called Megamolecules – where fusion proteins react with synthetic linkers to create multi-component, complex architectures. The modular megamolecule approach can position protein domains in configurations that are not accessible with traditional protein engineering techniques, including branched, cyclic, and dendritic structures, and can produce structures with dimensions that exceed 100 nm and molecular weights greater than 1 M Dalton. Synthesis of these complex structures is made possible by a highly efficient strategy for linking molecules together: the use of covalent inhibitors that react selectively and rapidly with their target enzyme domains. This approach greatly increases the rates and yields for conjugation compared to common bioconjugation techniques.  Currently, we are developing megamolecules for a diverse range of applications, including dynamic protein structures, materials, and antibody mimics that act as diagnostics and therapeutics.

Our group also developed SAMDI – an approach using MALDI mass spectrometry and arrays of self-assembled monolayers to perform quantitative experiments in high throughput. The arrays are prepared by immobilizing small molecules, proteins, peptides and carbohydrates on self-assembled monolayers of alkanethiolates on gold. These arrays are then treated with chemical reagents or enzymes and then analyzed using the SAMDI technique to measure changes in mass. This approach can detect a broad range of chemical reactions and enzymatic post-translational modifications – including the activities of kinases, proteases, methyltransferases and glycosyltransferases. We have used this platform for a wide range of studies, including the use of carbohydrate arrays to discover novel enzymes, the preparation of peptide arrays to profile the enzyme activities in cell lysates, and high-throughput screening to discover novel reactions and small molecule modulators.

Arthur Prindle

The overall goal of the Prindle Lab is to understand and engineer collective behaviors in microbial communities for synthetic biology applications

Emerging research of the human microbiome has generated new insights into the role of human-associated microbes in health and disease. In particular, microbes that colonize the gastrointestinal tract play a central role in host metabolism, immunity, and homeostasis, and can change in response to external perturbations such as dietary alterations, chemical exposures, and physiological or psychological stressors. However, the microbiome field currently lacks essential knowledge for how microbial cell-to-cell interactions give rise to higher-order community behavior, which is a key roadblock in the path towards next-generation microbiome-based products and therapies. The Prindle Lab is pursuing efforts to address these challenges, including developing multi-scale microfluidic platforms for microbial community analysis and contributing to the new field of bacterial electrophysiology. The overall goal is to decipher the underlying mechanisms of bacterial biofilm electrophysiology with the goal of better understanding and engineering natural microbial community behavior. These next-generation microbial community analysis and engineering tools provide a foundational platform for bridging synthetic biology technologies to the microbiome field.

Gabriel Rocklin

High-throughput protein biophysics and design

Proteins are gigantic molecules that perform nearly all of life’s essential functions: they break down your food, replicate your DNA, generate force for muscle contraction, capture light energy in photosynthesis, and identify viruses and other invaders in your body.

We are in the middle of a revolution in computational protein design — the science of creating new proteins for unmet needs in health care, materials, and energy. Still, huge goals remain out of reach, because we have so much more to learn about the physics of proteins.

Our lab develops new tools to study samples of thousands of different proteins mixed together. These large-scale experiments help us build a general understanding of protein physics, and to create more accurate, predictive computational models for protein design.

We also focus on designing improved protein therapeutics. By combining computational design with large-scale experiments, we can push beyond the limits of the proteins found in nature.

Amy Rosenzweig

To obtain an atomic level understanding of metalloprotein parts deployed in synthetic biology applications

Methanotrophic bacteria oxidize methane to methanol in the first step of their metabolic pathway. Methane is a potent greenhouse gas, with a global warming potential more than 84 times that of carbon dioxide over a 20-year period. Global warming presents a significant threat to human health, and as the only biological methane sink, methanotrophs have attracted much attention as a means of mitigating methane emissions. Moreover, vast natural gas reserves have led to renewed interest in bioconversion of methane. Whereas current industrial catalysts that can selectively activate the 105 kcal mol-1 C-H bond in methane require high temperatures and pressures, methanotrophs perform this chemistry under ambient conditions using methane monooxygenase (MMO) enzymes. The use of methanotrophs and these MMO biocatalysts thus provides an environmentally friendly alternative for methane conversion. The primary MMO in nature, particulate MMO (pMMO), is a three-subunit, integral membrane protein whose active site structure and chemical mechanism remain one of the major unsolved problems in bioinorganic chemistry. Any engineered pathway in methanotrophs for methane conversion to fuels or chemical feedstocks starts with methane conversion to methanol by pMMO. To be commercially viable, the speed and efficiency of pMMO must be improved, which requires a detailed understanding of pMMO structure and function. Current efforts in the laboratory are directed at elucidating the atomic details of the pMMO copper active site, understanding the mechanisms of dioxygen activation and methane oxidation, including how substrates, products, electrons, and protons access the active site, and probing the function of pMMO within the larger context of methanotroph physiology.

Danielle Tullman-Ercek

The DTE lab aims to understand and repurpose nanoscale self-assembling protein systems for applications in medicine, materials, and sustainability

We are interested in several key questions: 1) What fundamental principles govern the precise organization of proteins at the nanoscale? 2) How does organization of biochemical processes enhance their performance? 3) How can we manipulate these protein assemblies to gain new or enhanced functions in living and non-living systems? Our current model systems include protein containers such as the MS2 viral capsid and bacterial organelles called microcompartments, and membrane protein machines such as the type III secretion system. Each of these systems is important to understand, and offers a useful scaffold for including in engineered designs for sustainable chemical production, vaccines, drug delivery devices, and precision nanomaterials.

Our approaches to answer these questions are rooted in synthetic biology to take advantage of advances in high-throughput screening, next-generation DNA and protein sequencing, and systematic protein engineering. We couple these with deeper characterizations using microscopy, biochemical assays, cell-free reactions, chromatography, spectroscopy, and more.

We collaborate with a variety of other synthetic biologists, engineers, chemists, mathematicians, and materials scientists to tackle big problems that need creative solutions. We employ the design-build-test-learn method in almost every experiment, and we often team with computational collaborators to quickly learn and (re)-design for our next build and test steps of the cycle.

Keith Tyo

We are rewiring fundamental sensing/catalysis relationships to program cells

Microbes must cope with harsh, rapidly changing environments to survive. To do this, microbes have developed sophisticated mechanisms to (a) sense the changes in the environment, and (b) respond quickly to these changes to protect itself from harm or capitalize on an opportunity. Our lab seeks to rewire these fundamental sensing/catalysis relationships to program cells to do useful things for humankind in a paradigm called synthetic biology.

Sensing: We study methods to modify existing environmental detection sensors in yeast and modify them to detect new analytes.

Catalysis: We investigate ways microbes modify their metabolic networks and use these modifications to increase production of a given metabolite.

Sera Young

The Young Research Group seeks to better understand the determinants of healthy mothers and children across diverse geographical, cultural, and socioeconomic contexts

Household Water Insecurity

The ability to measure household food insecurity has been transformative, but our understanding of both how to measure household-level water insecurity and what its consequences are is in its early days. We are therefore exploring household water insecurity quantitatively and qualitatively in a number of sites around the world, and have discovered there are surprising and far-reaching ways that water insecurity shapes well-being.

Food Insecurity

What is the role of food insecurity in adverse maternal and child health and nutritional outcomes, especially in the context of HIV? What are the types of effects, the magnitude of effects, and which of these are modifiable? How can food insecurity be mitigated amongst women and children in low-resource settings? To answer these questions we have observational and intervention studies in Tanzania, Kenya, and Uganda.

Pica

Is pica an adaptive response to health challenges? What is the relationship between pica and iron deficiency? In our data from East Africa, North America, and elsewhere, we know that non-food cravings and iron deficiency are associated, but the nature of the relationship is unclear. We are using a variety of in vitro and in vivo animal studies, as well as observational cohorts, to ascertain the mechanisms underlying this relationship, and to test the two major physiological hypotheses about pica: supplementation and detoxification.