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 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)
- Profiling transcriptomic responses of human stem cell-derived medium spiny neuron-like cells to exogenous phasic and tonic neurotransmitters , MOLECULAR AND CELLULAR NEUROSCIENCE (2023)
- DINOS: Data INspired Oligo Synthesis for DNA Data Storage , ACM JOURNAL ON EMERGING TECHNOLOGIES IN COMPUTING SYSTEMS (2022)
- Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization , CELLS (2022)
- Modified Histone Peptides Linked to Magnetic Beads Reduce Binding Specificity , INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)
- DNA stability: a central design consideration for DNA data storage systems , NATURE COMMUNICATIONS (2021)
- Effects of early geometric confinement on the transcriptomic profile of human cerebral organoids , BMC BIOTECHNOLOGY (2021)
- Evaluation of UBE3A antibodies in mice and human cerebral organoids , SCIENTIFIC REPORTS (2021)
Grants
This proposal seeks to engineer new experimental platforms for chromatin biology.
The work combines optogenetics and single cell methods to analyze TF dynamics.
This project will engineer sensors of DNA methylation.
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.
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.
Human stem cell derived systems will be created to study the impact of genes lost in Angelman Syndrome.
There is substantial evidence that chromatin (genomic DNA and the proteins, RNAs, and chemical motifs bound to it) is a central regulator of diverse cellular and disease processes, in particular through its regulation of gene expression. Despite the wide-spread acceptance of its importance and relevance throughout biology, it is remarkable that our understanding of chromatin??????????????????s mechanisms and functions remains very limited and reliant on largely correlative observations or non-specific genome-wide perturbations. Here we propose the engineering of two synergistic and parallel sets of tools. One set of tools will sense and report on the dynamic biochemical and conformational states of chromatin in living mammalian cells. The other set of tools will dynamically induce changes in or ????????????????edit??????????????? chromatin biochemistry and conformation at specific user-defined genomic loci.
This proposal will develop new systems for practical DNA-based information storage systems.
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
- Genome Engineering and Synthetic Biology: Microbes
- Cellular and Molecular Genetics: Microbes
- Developmental Genetics: Vertebrate
- Cellular and Molecular Genetics: Vertebrates
- Genome Engineering and Synthetic Biology: Vertebrates