The Candida albicans acetylome in fungal virulence

真菌毒力中的白色念珠菌乙酰化组

基本信息

  • 批准号:
    9750616
  • 负责人:
  • 金额:
    $ 39.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-08-17 至 2021-07-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Lysine acetylation is one of the most prominent post-translational modifications (PTM) of proteins and has been recognized to play a key role in regulation of gene expression by histone modification and modulation of chromatin function. Despite impressive advances in our understanding of lysine acetyltransferases (KATs) and lysine deacetylases (KDACs) during the last decades, the role of reversible lysine acetylation in fundamental cellular processes in physiology and pathology from cancer to infectious diseases still remains poorly understood. In particular, the dissection of chromatin and non-chromatin functions of individual KATs/KDACs members still represents a major scientific challenge. For example, there is compelling evidence that lysine acetylation of proteins modulates virulence of pathogenic fungi such as Candida albicans, but the underlying mechanisms have remained largely unexplored. Understanding these mechanisms is all the more important because the recognition motifs of C. albicans acetyltransferases KATs are unique to the fungal kingdom and thus represent promising targets for antifungal drug discovery. The central hypothesis of the proposed research is that protein acetylation plays pivotal roles in controlling the cellular physiology and virulence of C. albicans. We formulated this hypothesis based on our preliminary data indicating that lysine acetylation is an abundant form of PTM in C. albicans. Furthermore, our previous work has implicated C. albicans Hat1, a paradigmatic histone lysine acetylase, in DNA damage repair, morphogenesis, biofilm formation, antifungal drug resistance, and virulence. However, the roles of several other lysine acetyltransferase enzymes in this organism have remained unknown. Our preliminary studies have also implicated acetylation at two specific lysine residues (K654 and K655) of Lig4, an important protein involved in Non-Homologous End Joining (NHEJ)-dependent DNA repair and modulating morphogenesis and virulence of C. albicans. Furthermore, new preliminary RNA-seq data suggest that Hat1 has important roles in mitochondrial function, as well as in the processing and regulation of non-coding RNAs (ncRNA). The main objective in our joint application is therefore to identify and characterize the histone and non-histone target genes of C. albicans Hat1 and to investigate its ill-defined role in regulation of mitochondrial function and a possible role in the NHEJ DNA repair. Guided by the preliminary data, we expect to test our central hypothesis and to accomplish the objectives of this application by pursuing the following three Specific Aims: 1) To identify and characterize both histone and non- histone (non-chromatin) targets of Hat1. 2) To investigate the possible role of acetylation of the NHEJ DNA repair pathway in regulation of C. albicans virulence. 3) To investigate role of Hat1 in the processing of ncRNA. The payoffs of this proposal are expected to be significant because we expect to uncover novel modes of regulation of key cellular processes important for pathogenesis of C. albicans.


项目成果

期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Transcriptome Signatures Predict Phenotypic Variations of Candida auris.
  • DOI:
    10.3389/fcimb.2021.662563
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    5.7
  • 作者:
    Jenull S;Tscherner M;Kashko N;Shivarathri R;Stoiber A;Chauhan M;Petryshyn A;Chauhan N;Kuchler K
  • 通讯作者:
    Kuchler K
The Two-Component Response Regulator Ssk1 and the Mitogen-Activated Protein Kinase Hog1 Control Antifungal Drug Resistance and Cell Wall Architecture of Candida auris.
  • DOI:
    10.1128/msphere.00973-20
  • 发表时间:
    2020-10-14
  • 期刊:
  • 影响因子:
    4.8
  • 作者:
    Shivarathri R;Jenull S;Stoiber A;Chauhan M;Mazumdar R;Singh A;Nogueira F;Kuchler K;Chowdhary A;Chauhan N
  • 通讯作者:
    Chauhan N
Identification of Genomewide Alternative Splicing Events in Sequential, Isogenic Clinical Isolates of Candida albicans Reveals a Novel Mechanism of Drug Resistance and Tolerance to Cellular Stresses.
白色念珠菌序列同基因临床分离株中全基因组选择性剪接事件的鉴定揭示了细胞应激耐药性和耐受性的新机制。
  • DOI:
    10.1128/msphere.00608-20
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    4.8
  • 作者:
    Muzafar,Suraya;Sharma,RaviDatta;Shah,AbdulHaseeb;Gaur,NaseemA;Dasgupta,Ujjaini;Chauhan,Neeraj;Prasad,Rajendra
  • 通讯作者:
    Prasad,Rajendra
Transcriptomics and Phenotyping Define Genetic Signatures Associated with Echinocandin Resistance in Candida auris.
  • DOI:
    10.1128/mbio.00799-22
  • 发表时间:
    2022-08-30
  • 期刊:
  • 影响因子:
    6.4
  • 作者:
  • 通讯作者:
Fungal KATs/KDACs: A New Highway to Better Antifungal Drugs?
  • DOI:
    10.1371/journal.ppat.1005938
  • 发表时间:
    2016-11
  • 期刊:
  • 影响因子:
    6.7
  • 作者:
    Kuchler K;Jenull S;Shivarathri R;Chauhan N
  • 通讯作者:
    Chauhan N
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

NEERAJ CHAUHAN其他文献

NEERAJ CHAUHAN的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('NEERAJ CHAUHAN', 18)}}的其他基金

Identifying drug-resistant Candida species using SuperSelective primer PCR
使用超选择性引物 PCR 鉴定耐药念珠菌种类
  • 批准号:
    10575446
  • 财政年份:
    2022
  • 资助金额:
    $ 39.75万
  • 项目类别:
The Candida albicans acetylome in fungal virulence
真菌毒力中的白色念珠菌乙酰化组
  • 批准号:
    9333188
  • 财政年份:
    2016
  • 资助金额:
    $ 39.75万
  • 项目类别:
Triazole hypersensitivity in Candida albicans
白色念珠菌的三唑超敏反应
  • 批准号:
    7494745
  • 财政年份:
    2008
  • 资助金额:
    $ 39.75万
  • 项目类别:
Triazole hypersensitivity in Candida albicans
白色念珠菌的三唑超敏反应
  • 批准号:
    7749806
  • 财政年份:
    2008
  • 资助金额:
    $ 39.75万
  • 项目类别:
Triazole hypersensitivity in Candida albicans
白色念珠菌的三唑超敏反应
  • 批准号:
    7567525
  • 财政年份:
    2008
  • 资助金额:
    $ 39.75万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了