Albert Keung
Bio
The sequencing of the human genome in 2001 was a milestone for science. However, the origins of most diseases and developmental processes remain obscure. It is now clear that beyond the genetic code there is a wealth of information stored in the dynamic organization of nuclear structures. This “epi-genetic” information controls how genes are accessed and expressed and is often misregulated in disease; yet, so far there have been few ways to synthetically read, write, and engineer it.
Drawing upon interdisciplinary approaches in engineering, biology, and physics our lab develops molecular technologies to expand and unlock new ways to control, understand, and harness chromatin. These technologies will enable researchers and engineers to manipulate features of chromatin, such as it’s biochemistry and 3-dimensional structure, in highly defined and specific ways. These technologies can be used to reveal the mechanisms of developmental transitions and diseases. In addition, they can be exploited to create synthetic “biological circuits” useful in applications such as antibody production and cancer-killing cells. Epigenetic control is a fundamental and ubiquitous aspect of cell biology; the ability to control its properties will unlock discovery and therapeutic opportunities in many areas of biology, medicine, and biotechnology.
Focus Areas – Synthetic Biology, Neural and Stem Cell Engineering, Bioengineering
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Publications
- A primordial DNA store and compute engine , Nature Nanotechnology (2024)
- Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities , Methods in Molecular Biology (2024)
- Single-Cell Assessment of Human Stem Cell-Derived Mesolimbic Models and Their Responses to Substances of Abuse , Organoids (2024)
- Summary of ChIP-Seq Methods and Description of an Optimized ChIP-Seq Protocol , Methods in Molecular Biology (2024)
- A molecular assessment of the practical potential of DNA-based computation , CURRENT OPINION IN BIOTECHNOLOGY (2023)
- Chaetocin disrupts the SUV39H1-HP1 interaction independent of SUV39H1 methyltransferase activity , BIOCHEMICAL JOURNAL (2023)
- FrameD: framework for DNA-based data storage design, verification, and validation , BIOINFORMATICS (2023)
- Matrigel Tunes H9 Stem Cell-Derived Human Cerebral Organoid Development , Organoids (2023)
- Profiling transcriptomic responses of human stem cell-derived medium spiny neuron-like cells to exogenous phasic and tonic neurotransmitters , MOLECULAR AND CELLULAR NEUROSCIENCE (2023)
- Reactive Oxygen Species Mediate Transcriptional Responses to Dopamine and Cocaine in Human Cerebral Organoids , International Journal of Molecular Sciences (2023)
Grants
This proposal seeks to engineer new experimental platforms for chromatin biology.
Digital information is being generated in excess of 1 zettabyte (1021 bytes) per year worldwide. Existing information storage technologies are reaching major limitations in keeping pace. These limitations include unsustainable increases in the demand for: information capacity, physical storage space, raw materials, and energy to cool and maintain storage systems. DNA, a natural medium of information storage in biological systems, has garnered excitement and attention from both academic and industry groups as a potential next generation storage technology. DNA offers several advantages including a raw capacity of 1 zettabyte per 1 cubic centimeter. In comparison, state of the art electronic storage media would require 1000 cubic meters to store the same information. DNA also exhibits exceptional stability with a half-life of over a hundred years at ambient temperatures and requires minimal energy to maintain. Thus, DNA could be a transformative information storage medium. This project considers the design of a DNA-based data storage system from a thermodynamics perspective, allowing us to fine-tune interactions between DNA strands to achieve high capacity, random access, and search.
The work combines optogenetics and single cell methods to analyze TF dynamics.
Angelman syndrome (AS) is a neurological disorder characterized by delayed development, intellectual disability, speech impairment, and ataxia1. The primary molecular driver defining AS is the loss of UBE3A protein in neurons, deriving from either mutation or deletion of maternal UBE3A, as the paternal allele is silenced in neurons. There have been exciting advances in identifying and developing potential therapeutics for Angelman Syndrome. In particular, a leading strategy has been to develop therapeutics that reactivate the paternal copy of UBE3A or that introduce an ectopic copy of UBE3A, with several exciting candidates in preclinical and clinical development. Despite these advances, important challenges remain: Challenge 1. It remains unclear the extent to which rescuing UBE3A expression in adults, children, or even infants will ameliorate the symptoms of AS. Challenge 2. High throughput experimental models for screening and validating therapeutics are currently unable to capture functional readouts at scale. Challenge 3. The human brain exhibits considerable and distinct genetic, cellular, and functional diversity between human genotypes and with rodent models. Challenge 4. Experimental models are needed that better mimic the human in vivo microenvironment. The primary goal of this proposed work is to develop a robust and scalable array of human organoids with embedded microelectrodes that can longitudinally track catecholamine and action potential changes over weeks to months, for downstream applications in drug screening.
This project will engineer sensors of DNA methylation.
This proposal will develop new systems for practical DNA-based information storage systems.
This is a fellowship proposal to enable the PI to pivot research directions to obtain new knowledge and expertise to enrich his research program.
This proposal will generate human cell lines to advance our understanding and treatment of ICD and UPD genotypes of Angelman Syndrome.
This is a proposal to establish models for testing candidate Angelman Syndrome therapeutics.
Human stem cell derived systems will be created to study the impact of genes lost in Angelman Syndrome.
Groups
- Biomedicine
- Cellular and Molecular Genetics
- Computational Genomics and Bioinformatics
- GGA Faculty: Department of Chemical and Biomolecular Engineering
- Developmental Genetics
- Environment
- Genome Engineering and Synthetic Biology
- GGA Faculty
- Biomedicine: Humans
- Genome Engineering and Synthetic Biology: Invertebrates
- Cellular and Molecular Genetics: Invertebrates
- Environment: Managed environments
- Cellular and Molecular Genetics: Microbes
- Genome Engineering and Synthetic Biology: Microbes
- Developmental Genetics: Vertebrate
- Cellular and Molecular Genetics: Vertebrates
- Genome Engineering and Synthetic Biology: Vertebrates