Evolution of Cargo Transport

货物运输的演变

基本信息

  • 批准号:
    10318674
  • 负责人:
  • 金额:
    $ 10万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-01-01 至 2023-12-31
  • 项目状态:
    已结题

项目摘要

Transporting cellular cargo with spatial and temporal precision is critical for many processes in all cells. Different cell types and organisms use diverse machineries for long-distance cargo transport. For example, mammalian cells and many filamentous fungi transport cargo using the microtubule-based motors dynein and kinesin, while yeast use myosin motors on actin cytoskeleton tracks. Despite a general understanding of cellular transport and the motors involved, little is known about how similar transport machineries are adapted by specific cell types or organisms. Dr. Christensen’s current research investigates canonical (motor-driven) and non-canonical cargo transport. In this proposal, she will investigate how both modes of transport have evolved in different organisms using an innovative approach in which evolutionary hypotheses are directly tested using comparative cell biology in fungal and mammalian cells. Defects in transport are particularly prevalent in neurological disorders such as Alzheimer’s, Huntington’s and ALS. Examining how diverse cell types differently use the transport machinery is directly applicable to understanding how transport defects lead to cell-specific diseases. In Aim 1, Dr. Christensen will investigate how regulators of motor-driven transport have evolved in fungi and human cells. In her current research and the K99 phase of this award, she will investigate how the gene expansion and functional diversification of the ‘FHF’ protein complex allows dynein to bind multiple cargos in human cells. For the R00 phase of this award, Dr. Christensen will identify and characterize novel dynein regulators using evolutionary analysis and comparative cell biology in A. nidulans and human cells. In Aim 2, Dr. Christensen will investigate a non-canonical form of transport known as ‘hitchhiking’. In hitchhiking, a cargo attaches to and is co-transported with another cargo to achieve motility. Hitchhiking has been demonstrated to occur in two evolutionarily divergent species of filamentous fungi, Aspergillus nidulans and Ustilago maydis. In the K99 phase of this award, she will investigate a potential evolutionary advantage of peroxisome hitchhiking in A. nidulans and determine if mRNA hitchhiking convergently evolved in A. nidulans and U. maydis. In the R00 phase of this award, she will determine if hitchhiking occurs in a third filamentous fungus, Ashbya gossypiii, a fungus lacking canonical microtubule-based transport. Dr. Christensen’s goal is to develop an independent research program at the interface of cell and evolutionary biology. To accomplish this, she will attend conferences spanning fields and participate in UCSD- sponsored and MOSAIC UE5 initiatives focused on lab management and the transition to independence. She will receive guidance from her mentoring committee (faculty listed below) and her primary mentor, Sam Reck- Peterson. This development plan, combined with training in evolutionary biology (with Matt Daugherty, UCSD), mammalian cell vesicle trafficking assays (with Susan Ferro-Novick, UCSD), and A. gossypii (with Amy Gladfelter, UNC Chapel Hill) will prepare her to excel in an independent position.
以空间和时间精度运输细胞货物对于所有细胞中的许多过程至关重要。不同 细胞类型和生物体使用不同的机械进行长距离货物运输。例如哺乳动物 细胞和许多丝状真菌使用基于微管的马达动力蛋白和驱动蛋白运输货物, 酵母在肌动蛋白细胞骨架轨道上使用肌球蛋白马达。尽管对细胞运输和 由于涉及电机,很少有人知道类似的运输机械是如何适应特定的细胞类型或 有机体克里斯滕森博士目前的研究调查规范(电机驱动)和非规范货物 运输在这个提议中,她将调查这两种运输方式是如何在不同的生物体中进化的 使用一种创新的方法,其中进化假说直接使用比较细胞生物学进行测试, 在真菌和哺乳动物细胞中。运输缺陷在神经系统疾病中特别普遍, 阿尔茨海默氏症,亨廷顿氏症和肌萎缩性侧索硬化症。研究不同的细胞类型如何不同地使用运输机制, 直接适用于理解运输缺陷如何导致细胞特异性疾病。 在目标1中,克里斯滕森博士将研究马达驱动运输的调节器如何在真菌中进化 和人体细胞。在她目前的研究和该奖项的K99阶段,她将研究基因是如何 “FHF”蛋白复合物的扩展和功能多样化允许动力蛋白结合多种货物 人类细胞。对于该奖项的R00阶段,Christensen博士将鉴定和表征新型动力蛋白 调节子,利用进化分析和比较细胞生物学在A. nidulans和人类细胞。 在目标2中,克里斯滕森博士将研究一种被称为“搭便车”的非规范形式的运输。在 搭便车,货物附着到另一货物并与另一货物共同运输以实现运动性。搭便车 已被证明发生在两种进化上不同的丝状真菌,构巢曲霉 和玉米黑粉菌(Ustilago maydis)。在该奖项的K99阶段,她将研究一种潜在的进化优势, 过氧化物酶体在A.并确定mRNA搭便车是否在A. nidulans 和联合玉米粉在该奖项的R00阶段,她将确定搭便车是否发生在第三个丝状 真菌,棉阿舒囊霉,一种缺乏典型的基于微管的运输的真菌。 克里斯滕森博士的目标是在细胞和生物学的界面上开发一个独立的研究项目, 进化生物学为了实现这一目标,她将参加跨领域的会议,并参加UCSD- 赞助和MOSAIC UE5计划侧重于实验室管理和向独立过渡。她 将接受她的指导委员会(以下列出的教师)和她的主要导师,山姆雷克的指导, 彼得森这个发展计划,结合进化生物学的培训(与马特·多尔蒂,加州大学圣地亚哥分校), 哺乳动物细胞囊泡运输测定(与Susan Ferro-Novick,UCSD)和A. gossypii(与艾米 格拉德费尔特,圣查佩尔山)将准备她在一个独立的位置出类拔萃。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Bidirectional lysosome transport: a balancing act between ARL8 effectors.
  • DOI:
    10.1038/s41467-022-32965-y
  • 发表时间:
    2022-09-07
  • 期刊:
  • 影响因子:
    16.6
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Jenna Christensen其他文献

Jenna Christensen的其他文献

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{{ truncateString('Jenna Christensen', 18)}}的其他基金

Hitchhiking is a novel mechanism of organelle transport
搭便车是细胞器运输的一种新机制
  • 批准号:
    9768484
  • 财政年份:
    2017
  • 资助金额:
    $ 10万
  • 项目类别:
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