Manjunatha Kogenaru- PhD
- Sr Scientist at NYU Langone Medical Center
Manjunatha Kogenaru
- PhD
- Sr Scientist at NYU Langone Medical Center
Gene, chromosome, and cell therapy innovations
About
30
Publications
15,972
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Introduction
I have over 15 years of PhD level research experience in gene network, protein, chromosome, and genome engineering. My core competencies include pioneering novel molecular technologies for protein and genome engineering. My goal is to develop innovative and transformative next generation therapies genetic diseases.
Current institution
Additional affiliations
November 2021 - present
NYU Grossman School of Medicine
Position
- Sr. Research Scientist
Description
- 1. Pioneering the development of engineered Zinc-Finger (ZF) technology to induce chromosome-specific missegregation, facilitating the creation of cancer cell models to study the mechanisms. 2. Bioinformatics analysis of various NGS data including functional CRISPR screening. 3. Contributed to the development of a next-generation gene editing strategy. 4. Contributed to the development of a universal deep-learning AI model for zinc-finger proteins.
Publications
Publications (30)
Naturally occurring DNA inversion systems play an
important role in the generation of genetic variation and
adaptation in prokaryotes. Shufflon invertase (SI) Rci from
plasmid R64, recognizing asymmetric sfx sites, has been adopted
as a tool for synthetic biology. However, the availability of a single
enzyme with moderate rates of recombination has...
DNA targeting Class 2 CRISPR-Cas effector nucleases, including the well-studied Cas9 proteins, evolved protospacer-adjacent motif (PAM) and guide RNA interactions that sequentially license their binding and cleavage activities at protospacer target sites. Both interactions are nucleic acid sequence specific but function constitutively; thus, they p...
To determine the chromosomal status of placentas after live birth following transfer of single mosaic embryos diagnosed by preimplantation genetic testing for aneuploidy (PGT-A).
The binary GAL4-UAS expression system has been widely used in Drosophila to achieve tissue-specific expression of genes. To further allow for simultaneous spatial and conditional control of gene expression in existing GAL4 expression lines backgrounds, temperature and chemical controllable GAL80 variants have been engineered. Here we add a new drug...
DNA targeting Class 2 CRISPR-Cas effector nucleases, including the well-studied Cas9 proteins, evolved protospacer-adjacent motif (PAM) and guide RNA interactions that sequentially license their binding and cleavage activities at protospacer target sites. Both interactions are nucleic acid sequence specific but function constitutively; thus, they p...
Cys 2 His 2 zinc finger (ZF) domains engineered to bind specific target sequences in the genome provide an effective strategy for programmable regulation of gene expression, with many potential therapeutic applications. However, the structurally intricate engagement of ZF domains with DNA has made their design challenging. Here we describe the scre...
Gene regulation networks allow organisms to adapt to diverse environmental niches. However, the constraints underlying the evolution of gene regulation remain ill defined. Here, we show that partial order—a concept that ranks network output levels as a function of different input signals—identifies such constraints. We tested our predictions by exp...
The limits of evolution have long fascinated biologists. However, the causes of evolutionary constraint have remained elusive due to a poor mechanistic understanding of studied phenotypes. Recently, a range of innovative approaches have leveraged mechanistic information on regulatory networks and cellular biology. These methods combine systems biol...
Gene regulation networks allow organisms to adapt to diverse environmental niches. However, the constraints underlying the evolution of regulatory phenotypes remain ill-defined both theoretically and experimentally. Here, we show that the concept of partial order identifies such constraints, and test the predictions by experimentally evolving an en...
Destabilizing domains (DDs) are genetic tags that conditionally control the level of abundance of proteins-of-interest (POI) with specific stabilizing small-molecule drugs, rapidly and reversibly, in a wide variety of organisms. The amount of the DD-tagged fusion protein directly impacts its molecular function. Hence, it is important that the backg...
Sign epistasis is a central evolutionary constraint, but its causal factors remain difficult to predict. Here we use the notion of parameterised optima to explain epistasis within a signalling cascade, and test these predictions in Escherichia coli. We show that sign epistasis arises from the benefit of tuning phenotypic parameters of cascade genes...
Supplementary Information
Sign epistasis caused by hierarchy within signalling cascades.
Nghe P, Kogenaru M, Tans SJ.
Nat Commun. 2018 Apr 13;9(1):1451. doi: 10.1038/s41467-018-03644-8.
PMID: 29654280
7 For the most part, contemporary proteins can be traced back to a basic set of a few thousand domain 8 prototypes, many of which were already established in the Last Universal Common Ancestor of life on 9 earth, around 3.5 billion years ago. The origin of these domain prototypes, however, remains poorly un-10 derstood. We have proposed that they a...
Contemporary proteins can be traced back to a basic set of a few thousand domain prototypes. The origin of these domain prototypes, however, remains poorly understood. We have proposed that they arose from an ancestral set of peptides, which acted as cofactors of RNA-mediated catalysis and replication. Their ability to fold was an emergent property...
Further supporting computational and experimental results.
(A) Sequence variation in RPS20-hh at positions 6, 7, 9 and 23 (TPR unit numbering) observed in RPS20 sequences. (B) Most commonly observed amino acids in RPS20-hh. (C) List of putative TPR homologs identified in the PDB by sequence and structure analysis. (D) RPS20-hh sequences that resemb...
Repetitive proteins are thought to have arisen through the amplification of subdomain-sized peptides. Many of these originated in a non-repetitive context as cofactors of RNA-based replication and catalysis, and required the RNA to assume their active conformation. In search of the origins of one of the most widespread repeat protein families, the...
Many of the gene regulatory networks used within the field of synthetic biology have extensively employed the AraC and LacI inducible transcription factors. However, there is no Escherichia coli strain that provides a proper background to use both transcription factors simultaneously. We have engineered an improved E. coli strain by knocking out th...
To what extent biochemical parameters and topology of a network changes during adaptation processes is unclear. To address this, we constructed a synthetic regulatory cascade that controls the expression of tunable cost-benefit operon using well-characterized repressors. We evolve this network towards the goals specified as desired input-output rel...
We study the evolution of a regulatory network in heterogeneous environments: a synthetic cascade controls the expression of enzymes providing a cost or a benefit for the bacteria. We measure the outcome of natural selection performed on mutant pools in different complex environments, combining cues and ressources which independently impact express...
Insight into the ruggedness of adaptive landscapes is central to understanding the mechanisms and constraints that shape the course of evolution. While empirical data on adaptive landscapes remain scarce, a handful of recent investigations have revealed genotype-phenotype and genotype-fitness landscapes that appeared smooth and single peaked. Here,...
Determining the course of adaptation in variable environments remains a fundamental issue in evolutionary biology. Such an adaptation process is governed by intriguing relationships between genotype, phenotype, fitness and environment. Quantitative understanding of these relations is often difficult in naturally occurring systems. Therefore, by usi...
Advancement in the field of synthetic, molecular, and quantitative biology allows the construction of synthetic gene regulatory networks using model regulatory proteins and DNA regulatory regions, and to measure their behaviour quantitatively in vivo. We constructed a synthetic regulatory cascade that controls the expression of three different fluo...
The concept of epistasis has since long been used to denote non-additive fitness effects of genetic changes and has played a central role in understanding the evolution of biological systems. Owing to an array of novel experimental methodologies, it has become possible to experimentally determine epistatic interactions as well as more elaborate gen...
Advancement in the field of synthetic, molecular, and quantitative biology allows the construction of synthetic gene regulatory networks using model regulatory proteins and DNA regulatory regions, and to measure their behavior quantitatively in vivo. We constructed a synthetic regulatory cascade that controls the expression of three different fluor...
Solenoid repeat proteins of the Tetratrico Peptide Repeat (TPR) family are involved as scaffolds in a broad range of protein-protein interactions. Several resources are available for the prediction of TPRs, however, they often fail to detect divergent repeat units.
We have developed TPRpred, a profile-based method which uses a P-value-dependent sco...
Tetratricopeptide repeat (TPR) is formed of two or more stacked aa-hairpins. TPR-like domains might have arisen from the repetition of protein fragments. We have identified several promising aa-hairpins in globular proteins that are similar in sequence and structure, from which we are interested to engineer perfectly repetitive TPR proteins
Questions
Questions (3)
Please could anyone direct me to a company that provides a service for yeast-display selection of Nanobody variants from synthetic or naïve libraries?
I see majority of companies use phase display for selection of functional variants from synthetic/ naïve/immune libraries. I would highly appreciate if anyone can direct me to a company that offers yeast display selection on synthetic/naïve libraries.
Many thanks for your help!
Anyone tried to express a transgene from a native 5’LTR promoter of the lentiviral system. Literature says that 5' LTR promoter is inactivated upon integration into the target genome to prevent the replication of the viral sequences.
My transgenes are quite large (total viral genome from 5’ LTR to 3’ LTR: 5-11 kb with introns, and 5-9 kb upon splicing). I am not able to produce any functional viral particles above 5 kb size. Hence exploring on the possibility to reduce the overall genome size. In this regard, I am thinking of removing the CMV promoter used to drive the transgene and then relay on the 5’ LTR promoter to drive the transgene.
Any suggestions in this regard would be highly appreciated.
Many thanks
Manjunatha
Please could someone suggest me a source for mouse or human TTFs cell line with Oct4-neomycin or Nanog-neomycin selection marker.
I am aware of the transgenic mice sources carrying a drug-resistant selection marker, but I am looking for a cell line that I can buy directly from a company or an organization.
Many thanks
Manjunatha
