Kyoto University · Biochemistry, Genetics and Molecular Biology
간يش N. 파디안 교수의 연구실은 에피제네틱스와 합성 생물학을 융합한 혁신적 연구를 수행하고 있습니다. 주요 연구 방향은 특정 DNA 서열을 정밀하게 타겟팅하는 페릴-이미다졸 폴리아미드(PIPs)를 활용해 유전자 발현을 제어하는 인공적 에피제네틱 스위치를 개발하는 것입니다. 특히, SAHA와 같은 히스톤 디아세틸화 억제제를 결합한 'SAHA-PIPs'를 통해 간단한 화합물로도 만성세포의 다능성 유전자를 활성화하는 데 성공했으며, 이는 재프로그래밍 기반 줄기세포 생성의 효율성을 극대화하는 데 기여합니다. 최근에는 AI 기반의 오미크스 데이터 분석을 접목해 자연물에서 유래하는 신규 에피제네틱 작용 물질을 탐색하고 있습니다.
Figures are computed from collected data and may differ slightly.
ABSTRACT According to the World Health Organization (WHO), the coronavirus (COVID-19) pandemic is putting even the best healthcare systems across the world under tremendous pressure. The early detection of this type of virus will help in relieving the pressure of the healthcare systems. Chest X-rays has been playing a crucial role in the diagnosis of diseases like Pneumonia. As COVID-19 is a type of influenza, it is possible to diagnose using this imaging technique. With rapid development in the
Cellular reprogramming involves profound alterations in genome-wide gene expression that is precisely controlled by a hypothetical epigenetic code. Small molecules have been shown to artificially induce epigenetic modifications in a sequence independent manner. Recently, we showed that specific DNA binding hairpin pyrrole-imidazole polyamides (PIPs) could be conjugated with chromatin modifying histone deacetylase inhibitors like SAHA to epigenetically activate certain pluripotent genes in mouse
The influential role of the epigenome in orchestrating genome-wide transcriptional activation instigates the demand for the artificial genetic switches with distinct DNA sequence recognition. Recently, we developed a novel class of epigenetically active small molecules called SAHA-PIPs by conjugating selective DNA binding pyrrole-imidazole polyamides (PIPs) with the histone deacetylase inhibitor SAHA. Screening studies revealed that certain SAHA-PIPs trigger targeted transcriptional activation o
Covering: up to the end of 2022Microorganisms are exceptional sources of a wide array of unique natural products and play a significant role in drug discovery. During the golden era, several life-saving antibiotics and anticancer agents were isolated from microbes; moreover, they are still widely used. However, difficulties in the isolation methods and repeated discoveries of the same molecules have caused a setback in the past. Artificial intelligence (AI) has had a profound impact on various r
Abstract In the natural cellular environment, nucleic acid biomolecules like DNA have biological implications via structural modifications and through precise coordination with other biomolecules in the local environment. Here, we detail the design of nature-inspired smart biomaterials that are based on the chemical biology of nucleic acids. N-Methylpyrrole (P) and N-methylimidazole (I) polyamides (PIPs), sequence-specific DNA-binding molecules have been, developed to image specific DNA sequence
Considering the essential role of chromatin remodeling in gene regulation, their directed modulation is of increasing importance. To achieve gene activation by epigenetic modification, we synthesized a series of pyrrole-imidazole polyamide conjugates (PIPs) that can bind to predetermined DNA sequences, and attached them with suberoylanilide hydroxamic acid (SAHA), a potent histone deacetylase inhibitor. As histone modification is associated with pluripotency, these new types of conjugates, terme
A nontransgenic approach to reprogram mouse somatic cells into induced pluripotent stem cells using only small molecules got achieved to propose a potential clinical-friendly cellular reprogramming strategy. Consequently, the screening and identification of small molecules capable of inducing pluripotency genes in human cells are increasingly a focus of research. Because cellular reprogramming is multifactorial in nature, there is a need for versatile small molecules capable of modulating the co
The epithelial cell membrane 252-kDa protein (P252) isolated in our laboratory from Bombyx mori midgut was shown to bind strongly with Cry1Aa, Cry1Ab, and Cry1Ac toxins of Bacillus thuringiensis (15). In the current paper, P252 was shown to bind with chlorophyllide (Chlide) to form red fluorescent protein (RFP) complex, termed Bm252RFP, with absorbance and fluorescence emission peaks at 600 nm and 620 nm, respectively. P252 at a concentration of 1 microM is shown to bind with about 50 microM Chl
Telomeres are closely associated with cellular senescence and cancer. Although some techniques have been developed to label telomeres in living cells for study of telomere dynamics, few biocompatible near-infrared probes based on synthetic molecules have been reported. In this study, we developed a near-infrared fluorogenic pyrrole-imidazole polyamide probe (<b>SiR-TTet59B</b>) to visualize telomeres by conjugating a silicon-rhodamine (<b>SiR</b>) fluorophore with a tandem tetramer pyrrole-imida
Transcriptional activators play a central role in the regulation of gene expression and have the ability to manipulate the specification of cell fate. Pluripotency is a transient state where a cell has the potential to develop into more than one type of mature cell. The induction of pluripotency in differentiated cells requires extensive chromatin reorganization regulated by core transcriptional machinery. Several small molecules have been shown to enhance the efficiency of somatic cell reprogra
Natural epigenetic processes precisely orchestrate the intricate gene network by expressing and suppressing genes at the right place and time, thereby playing an essential role in maintaining the cellular homeostasis. Environment-mediated alteration of this natural epigenomic pattern causes abnormal cell behavior and shifts the cell from the normal to a diseased state, leading to certain cancers and neurodegenerative disorders. Unlike heritable diseases that are caused by the irreversible mutati
The potential biotechnological uses of bat-associated bacteria are discussed briefly, indicating avenues for biotechnological applications of bat-associated microbes. The uniqueness of bats in terms of their lifestyle, genomes and molecular immunology may predispose bats to act as disease reservoirs. Molecular phylogenetic analysis has shown several instances of bats harbouring the ancestral lineages of bacterial (<i>Bartonella</i>), protozoal (<i>Plasmodium</i>, <i>Trypanosoma cruzi</i>) and vi
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