Please join us October 4th for a virtual scientific symposium and celebration of CZ Biohub’s first five years of innovation and discovery, featuring keynotes from NIH Director Francis Collins and others.
The CZ Biohub Investigator Program is funding research by world-renowned scientists, engineers, and technologists from UC Berkeley, Stanford University, and UCSF. This funding is unrestricted, giving these extraordinary Investigators the freedom to pursue their riskiest, most exciting ideas. Many of these high-risk projects will involve the invention of new tools and techniques that accelerate the pace of scientific discovery and help CZ Biohub realize its vision of curing, preventing, or managing every disease by the end of the century.
The Intercampus Research Awards have supported cutting-edge research for collaborative, multi-institution teams. Each cross-disciplinary team includes talented faculty members from our three partner universities of UCSF, UC Berkeley, and Stanford University. By working together, these talented investigators have developed new technologies and advance our understanding of some of the most demanding challenges in biomedical research.
CZ Biohub continues to build its cross-disciplinary scientific community and accepts applications annually for new cohorts of the Chan Zuckerberg Biohub Investigator Program. Submissions for early-stage, high-risk research proposals for the Investigator Competition 2021 closed on Friday, May 14.
Abate builds new technologies to enable complex biological systems to be understood quantitatively and comprehensively, as illustrated by his development of the picoinjector to inject very small volumes of reagents into droplets at high rates. He is now developing ways of printing organ-like structures by the precise placement of different cell types at defined positions.
Banfield is uncovering the vast diversity of microorganisms that depend on coexisting microbial community members for most core metabolic resources, and has discovered two major evolutionary radiations, one in bacteria and the other in archaea. She is exploring the medical, industrial, and ecological significance of these newly found microorganisms.
Barnes combines biophysical methods with in vivo approaches to understand how viruses such as HIV and SARS-CoV-2 infect host cells and elicit specific humoral immune responses. His research will translate knowledge of the structural correlates of antibody-mediated neutralization of viruses into the rational development of highly protective antibodies. A related goal is the structure-based design of potent and stable immunogens for vaccination.
Bateup’s research is elucidating the cellular and molecular basis of neurological and psychiatric disease. Her goal is to generate a mechanistic understanding of how disease-associated mutations affect neuronal biology and physiology, and how altered neuronal activity impacts circuit function and behavior. In addition, she is investigating the early alterations that contribute to neurodevelopmental disorders using genetically engineered human brain organoids.
Blish aims to build an atlas of host-pathogen interactions to serve as a template to elicit immune responses that will promote pathogen eradication. She seeks to understand how to control the innate immune response mediated by natural killer cells and other cells to eliminate infections and develop more potent methods of protection.
Booth pioneers the development of genetic tools in choanoflagellates to discover how these microeukaryotes regulate gene expression and cellular architecture to transition between different cell states in response to their environment. He aims to synthesize a molecular understanding of these cell-state transitions with evolutionary history to fathom the origins and evolution of cell identity and cell fate in choanoflagellates and their closest living relatives, the animals.
Buchwalter studies the mechanisms that govern the maintenance, remodeling, and specialization of nuclear organization across cell types. Her work is uncovering relationships between nuclear bodies such as the nuclear lamina and the nucleolus, and is defining how nuclear organization is disrupted by aging and disease.
Bustamante is making a transition from population genetics to a new area, the integration and analysis of massive data coming from consumer, health care, and financial sources. He is especially interested in bringing together direct-to-consumer genetics and phenotype data in a secure space that can be explored by academic, industry, and citizen scientists.
Chou studies the mechanisms driving tick-borne transmission of bacterial pathogens, such as Borrelia burgdorferi, the causative agent of Lyme disease. She would like to understand why only certain tick species are capable of transmitting these bacteria, with the goal of identifying new strategies for blocking the cycle of infection.
Clarke investigates the molecular regulation of stem cell regeneration (self-renewal) in normal and diseased tissue. His laboratory has generated novel tools to define epigenetic regulators of stem cell self-renewal. He is using these tools to elucidate how self-renewal pathways are modified in cancer and degenerative diseases such as Alzheimer’s disease, Down syndrome, osteoporosis, and diabetes mellitus.
De la Zerda’s goal is to image 100 million cells in living tissues at single-cell resolution by using optical coherence tomography. One of the potential uses of his technique will be to visualize cancer markers to delineate the margins of tumors.
Dumont is interested in how the properties of individual molecules give rise to the mechanics and function of large cellular machines. She focuses on the machines that drive cell division, asking how they build themselves through self-organization and how they generate and respond to mechanical force to perform their function robustly and accurately.
El-Samad analyzes the control of feedback loops, a fundamental underpinning of life, to understand their interconnected architecture and predict their failure modes in disease. She is embarking on a major effort to build de novo synthetic circuits consisting of biomolecules that can implement feedback control on demand.
Fletcher studies how cells assemble molecular-scale parts into micron-scale structures necessary for cell motility, cell-cell signaling, and host-pathogen interactions. He plans to launch a new effort to map the topography and spatial organization of cell-cell surfaces, starting with macrophages in their interactions with tumor cells.
Fordyce is developing new biochip technologies for high-throughput functional characterization of proteins to enhance our ability to predict the function of a protein given its amino acid sequence. Her aim is to characterize the properties of more than a thousand proteins, such as enzymes and transcription factors, in a single experiment.
Frost uses atomic-resolution cryo-electron microscopy in concert with biochemistry, genetics, and live imaging to advance our understanding of how cellular machines function normally, how they are corrupted by disease, and how they are hijacked by infectious pathogens. His studies of protein quality control may lead to new targets for the therapy of infectious diseases.
Frydman uses multidisciplinary approaches to gain a comprehensive understanding of the complex networks mediating protein homeostasis, the maintenance of protein quality. She plans to map the proteostasis network involving more than a thousand proteins and use this information to develop a new class of therapeutic agents for dengue, Zika, and other viral diseases.
Gartner aims to define the rules used by cells to self-organize into structurally ordered tissues and to reveal how tissue structure guides the flow of information between cells to coordinate decisions and behaviors. He is developing a system to quantitatively measure how the local density of mesenchymal cells and their tractions affects the curvature of overlying tissue.
Gawad works at the interface of biotechnology, computational biology, cellular biology, and clinical medicine to develop and apply new tools for characterizing genetic variation across single cells within tissue with unparalleled sensitivity and accuracy. He is applying these technologies to study the clonal evolution of cancer to facilitate the identification of treatment-resistant genotypes – to better understand and predict treatment response – and to study the development of increased virulence and drug resistance in bacteria and viruses
Goldberg studies how the coordination of immunity and metabolism regulates inflammation. She has focused on how metabolic programs determine immune function and how this influences metabolic health and inflammatory disease. Goldberg also seeks to understand how the changing tissue microenvironment impacts the aging immune system.
Greenhouse addresses fundamental questions about the transmission of malaria to better target and evaluate interventions for controlling the disease, combining field studies in infected areas with advanced molecular genetic studies in the laboratory. He is using more sensitive parasite detection and genotyping methods to track infections and screening for malaria-specific antibodies as a record of past exposure.
Greenleaf studies the physical and spatial organization of the human genome at multiple scales and across different biological states. His aim is to unravel the quantitative relations between regulatory elements and gene expression in a massively parallel way to generate a quantitative model of the regulatory wiring of cells.
Gunaydin seeks to elucidate the cellular and circuit mechanisms underlying major psychiatric diseases. She is carrying out optogenetic studies of a genetic mouse model of obsessive-compulsive disorder to elucidate patterns of abnormal neural activity as a first step in intervening to restore normal behavior.
Harwell studies how the extensive morphological, molecular, and functional diversity of neural cell types is achieved during development of the central nervous system. He focuses on the forebrain, with the long-term goals of understanding how genetic and epigenetic programs associated with the spatial and temporal identity of progenitor cells dictate their developmental trajectories, and how diverse groups of neurons and glia coordinate to assemble the precise circuitry of the mammalian forebrain during development.
Herr is designing, developing, and disseminating tools to quantify biological complexity, from the level of biomolecules to tissues, using novel engineering approaches. She is focusing on protein cytometry, as exemplified by single-cell electrophoresis followed by antibody probing to simultaneously achieve high specificity and high sensitivity.
Hockemeyer focuses on establishing reliable techniques to model human diseases using genetically engineered human stem cell models, human organoid systems, and genetic mouse models. Leveraging these methods with his expertise in telomere biology, he seeks to understand the consequences of telomere shortening in adult stem cells and how this impacts tumor formation, stem cell renewal, long-term tissue renewal, and organismal aging.
Huang has visualized the dynamics of chromosomal organization with multicolor imaging and has developed super-resolution microscopic methods for mapping proteins in key cellular structures. He plans to develop a fluorescence microscopy-based approach for the discovery and characterization of cell signaling networks, particularly those involving G-protein coupled receptors.
Jerby-Arnon studies multicellular dynamics, as a disease driver and therapeutic avenue, focusing on the interplay between cancer and immune cells. Fusing single-cell technologies with machine learning, imaging, and genetic editing, she develops integrative approaches to decipher, monitor, and trigger multicellular cascades, aiming to identify new and more effective ways to block tumor formation and progression.
Kampmann’s goal is to understand the molecular mechanisms driving neurodegenerative diseases such as Alzheimer’s and Parkinson’s. He is developing cell-based models of neurodegenerative disease processes in human induced pluripotent stem cells and is carrying out CRISPRi screens to identify underlying neuron-specific processes.
Kim is a CZ Biohub Senior Investigator and known for discovering how proteins cause viral membranes to fuse with cells. He has designed novel compounds that stop membrane fusion by HIV and has pioneered efforts to develop an HIV vaccine based on similar principles. At the CZ Biohub, Kim leads the Infectious Disease Initiative, which aims to explore new approaches and invent new tools for creating diagnostic tests, drugs, vaccines, and rapid-response strategies to support the global fight against both existing and newly emerging infectious diseases.
Kobilka’s pioneering X-ray crystallographic studies have revealed how the binding of a hormone to the extracellular pocket on a G-protein coupled receptor is transmitted across the cell membrane to trigger a signaling cascade. He is now carrying out structural studies of opioid receptors to identify more effective painkillers with fewer side effects.
Konermann develops and applies technologies for high-throughput transcriptional perturbations to understand the cellular and molecular pathways driving human genetic risk in neurodegenerative disease
Kortemme is developing a platform technology to computationally engineer novel biological components that convert the sensing of diverse and currently undetectable small-molecule signals into cellular responses. She is devising ways of making CRISPR-based gene editing switchable by small molecules.
Landry is developing new nanosensor technology and near-infrared imaging platforms to visualize neurotransmitters in the living brain at high spatial and temporal resolution. She will focus on deep brain imaging of dopamine as an initial step in furthering our understanding of psychiatric disorders.
Leskovec studies massive complex networks at a very wide range of scales, from interactions of proteins in a cell to interactions between humans in a society. He is devising new computational network tools to enhance patient care through social support, facilitate the diagnosis of disease by wearable sensors, and promote positive behaviors conveyed by social networks.
Listgarten works at the intersection of machine learning, statistics, and molecular biology. Problem domains of interest to her include genetics, epigenetics, immunology, proteomics, gene editing, and rational protein engineering. She develops new computational and machine learning methods to uncover data-driven insights from complex systems, along with corresponding tools for others to use.
Madhani is exploring whether cells maintain epigenetic memory, mediated for example by the methylation of cytosine residues in DNA, over evolutionary timescales. He is characterizing extant DNA methyltransferases, particularly those involved in fungal virulence, to trace their evolution and engineer cellular memory devices.
Maharbiz explores the ways that miniaturized technology and biology can be threaded together to create novel clinical devices that interface with the human body and provide real-time information about molecular and physiological states. He invented neural dust as a general platform for reading and writing data to tiny (~100 micrometer) implants that are activated by ultrasound.
Marqusee uses biophysical approaches to understand the information encoded in a protein sequence that governs protein dynamics and folding. She plans to develop new high-throughput methods to characterize the effect of changes in sequence and environment on protein function with the aim of enabling more precise predictions of the biological effects of genetic mutations and other sequence variants.
Marson is developing genome editing technologies to understand how sequence variation in the human genome alters and controls T cell immune function. He aims to engineer a new generation of targeted therapies for autoimmune disorders, immunodeficiencies, and infectious diseases.
Muller is developing new wireless microsystems that directly interface with the brain for long-term, minimally invasive neurological recording. Her broad goal is to engineer novel implants that can simultaneously sense and alter physiological responses to enable drug delivery and the treatment of neuropsychiatric disorders.
Olzmann investigates the molecular mechanisms that govern cellular lipid homeostasis. His work is advancing our understanding of the biogenesis, regulation, and functions of neutral lipid storage organelles called lipid droplets. He is interested in leveraging systems-biology approaches to uncover how cells protect themselves from lipotoxic damage, which could lead to novel therapeutic strategies to ameliorate degenerative conditions or to combat cancer.
Pollard studies the microbiome of humans, the microorganisms and viruses we harbor, to determine its role in shaping the health of people and their responses to therapeutic agents. Her laboratory has just released prototype open-source software that quantifies microbial population genetic variation using metagenomics data and will scale it for use by hospitals.
Poon aims to find new ways of miniaturizing bioelectronic devices, targeting specific neural circuits in vivo, and supporting closed-loop monitoring and manipulation of neural circuits. Her bioelectronics platform integrates electrical stimulation and recording with optogenetic stimulation, and will be used to study neural circuits in a mouse model of Alzheimer’s disease.
Porteus uses genome editing as curative therapy for genetic diseases, as exemplified by his correction of the mutation in sickle cell disease in hematopoietic stem and progenitor cells. He is now combining genome editing with synthetic biology to engineer cells having new phenotypic properties, such as engineering resistance to HIV and enhancing wound healing.
Prakash develops measurement tools, such as ultra-low-cost microscopy platforms for field diagnostics of infectious diseases, for use in extreme resource-poor areas of the world. His aim is to devise new frugal platforms for the diagnosis and surveillance of schistosomiasis, leishmaniasis, and malaria.
Reiter investigates how eukaryotic cells build cilia and how cilia function in intercellular communication. His work has helped to reveal how cilia signal, including the role of regulated trafficking of transmembrane proteins in and out of cilia, how cilia coordinate intercellular communication, and how defective ciliary signaling contributes to diseases, including specific cancers.
Rosenberg uses structural biology and microbial genetics to discover and exploit molecular vulnerabilities in bacteria for the development of next-generation therapeutics. He focuses on bacterial virulence systems that mediate interactions with the mammalian host in his search for new targets.
Roybal explores how T cells orchestrate a vast signaling network during their activation in the immune response. He will focus on the dynamics of synthetic Notch receptors and other signaling domains to devise new ways of controlling immune function in cancer therapy.
Sattely merged engineering and detailed knowledge of plant biochemical pathways to enhance human health. Her specific goal was to engineer strains of the most widely consumed dietary plants, such as maize and wheat, to improve their nutrient content.
Sanulli studies the organizing principles of the genome and how these principles regulate cell identity. She combines biophysical methods with in vivo approaches to explore genome organization and dynamics across length and time scales. By understanding how cells leverage the diverse biophysical properties of chromatin, she aims at understanding the link between genome compartmentalization and function in health and disease.
Seed carries out epidemiologic studies of the interactions between bacteriophages and Vibrio cholera in samples obtained from cholera outbreaks to enhance our understanding of how these viruses shape the communities of these pathogens and affect infectivity. She will also determine how microclimates impact phage-host interactions.
Sello develops chemical tools for studies of complex biological phenomena with an eye toward their translation into next-generation therapeutics. Molecules of greatest interest are those that have the potential to advance our understanding and treatment of infectious diseases, cancer, and neurological disorders. He has recently identified small molecules that perturb protein homeostasis and trafficking in ways that kill pathogens or suppress their infectivity.
Shapiro has established the bacterium Caulobacter crescentus as a powerful model organism for understanding self-organization and spatially controlled differentiation leading to daughter cells with different cell fates. She is developing a reaction-diffusion model that includes all essential cellular processes to gain a deeper understanding of asymmetric cell division and cell polarity.
Smolke is engineering yeast to produce complex, valuable plant-inspired medicinal compounds like those widely used as antihypertensives and anticancer agents. She interacts with experts in plant-specialized metabolism to identify gene clusters that can be inserted into her optimized yeast platform to accelerate the discovery of new therapeutic agents.
Soh has devised sensors capable of continuously monitoring specific biomolecules in vivo and a control system for achieving real-time, closed-loop, controlled drug delivery in live animals. He plans to generate detection systems for hitherto untargetable biomolecules and to develop real-time sensors that can be implanted in vivo to detect multiple biomolecules that are medically important.
Song has derived novel mathematical formulas and new analytical techniques for inferring demographic history from population genetic data and increasing the power of genome-wide natural selection scans. He is using new probabilistic models to elucidate the dynamics of protein initiation and elongation on ribosomes, and has recently moved into computational immunology.
Spitzer investigates how immune responses are coordinated across cell types, time, and space. His lab uses single-cell analysis and computational biology to build models of the immune system and its dynamics during challenges, including cancer and infection.
Streets is developing optical and microfluidic methods to carry out chemical and transcriptional profiling of single cells in whole tissues with preservation of positional information. He is using stimulated Raman scattering microscopy for determining chemical composition and laser-assisted microfluidics for transcriptional profiling.
Ting develops, scales up, and broadly disseminates molecular technologies for mapping cells and functional circuits, as illustrated by her biotin-based method for protein mapping in living cells. She is devising methods for identifying the ensemble of neurons that encode or control a specific memory, behavior, or emotional state by using a light- and calcium-gated transcription factor.
Waller’s goal is to develop simple and inexpensive microscopes that can image previously inaccessible information using computational microscopy, the joint design of imaging system hardware and software. She is now working on the challenging problem of 3D imaging in scattering media, such as deep structures of the brain, essential for unraveling neural activity.
Wang studies human immunity and susceptibility to viral pathogens such as dengue virus. Her research is driven by the finding that humans have diverse immunoglobulin Fc domains that affect the severity of viral diseases and the effectiveness of vaccines.
Wells is tackling the fundamental question of how cells remodel their surface proteomes, encoded by about 3000 genes, in response to changes in state, disease, and therapeutic intervention. He is developing robust quantitative proteomics methods for profiling cell surfaces and generating recombinant antibodies to membrane proteins on an industrialized scale to address this challenge.
Williams studies interacting networks of bacterial nanomachines that sustain life through cellular communication. With atomic-level insights, she aims to elucidate the connectivity between macromolecular machines used for cell wall biogenesis, adaptation, stress response, and virulence. This work should establish new paradigms for understanding the crosstalk between cellular nanomachines that can be exploited for drug discovery to fight antibiotic resistance.
Xu is developing novel super-resolution microscopy methods with a resolution below 10 nm that are revealing new ordered structures, such as a periodic cytoskeleton in nerve axons. His next step is to obtain functional information from super-resolution microscopy by combining it with multi-color fluorescence spectroscopy.
Yeh studies the apicoplast, a unique organelle in Plasmodium falciparum parasites, to identify new targets for the prevention and therapy of malaria. She aims to comprehensively identify the apicoplast proteome and understand the novel biogenesis pathways of this unusual plastid in her search for novel therapeutic targets.
Yosef uses computational tools to understand how transcription is regulated in mammalian cells and to learn how changes in transcription are associated with different cell-states or diseases. He seeks to develop data-driven approaches for defining the key factors that contribute to cell-to-cell variability with a focus on the cellular diversity of the immune system.
Zhang is engineering the biosynthesis of natural products by exploiting novel enzymatic machinery for synthesizing many unique pharmacophores and molecular scaffolds. She is developing a general platform for the in situ tagging of natural product mixtures to enable subsequent visualization by fluorescence imaging or stimulated Raman scattering microscopy.
Zou develops novel machine learning tools that enable researchers to make complex predictions and quantify disease mechanisms using population genomics and epigenomics data. He is devising new deep learning models to increase the accuracy of predicting genetic risk from genotypes and of identifying distinct cell populations based on single cell transcriptional profiles.
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