Danielle Grotjahn, PhD
Scripps Research Joint Appointments
Research Focus
The Grotjahn lab research program focuses on understanding how mitochondrial networks change shape in response to genetic, pharmacological, or environmental stress. By utilizing multidisciplinary imaging techniques, including cellular cryo-electron tomography (cryo-ET) and correlative light and electron microscopy (CLEM), our lab exposes the uncharted depths of cellular landscapes to define how the precise organization subcellular structures regulates mitochondrial homeostasis, and how disruptions to these molecular interactions gives rise to disease pathogenesis.
Research Description
Although commonly referred to as “Powerhouses of the Cell” for their role in metabolism and ATP generation, mitochondria are also expert “Stress Sensors of the Cell”, reflecting their contribution as a central hub for integrating several cell stress pathways. Interestingly, mitochondrial networks undergo dramatic morphological remodeling in response to varying stress conditions, and in this manner, mitochondrial shape can be used as a readout for overall cellular health. In fact, a hallmark feature of many neurodegenerative diseases is the presence of mitochondria with severely altered morphologies that reflect their impaired function. Although the link between altered mitochondria and disease pathology is well established, the cellular mechanisms that facilitate mitochondrial shape changes that lead to organellar and cellular dysfunction remain poorly defined.
In the Grotjahn Lab, we are interested in studying the functional and structural interactions that mediate these stress-induced modulations to mitochondrial networks using techniques that directly bridge the intersection between cellular, molecular, and structural biology fields, including whole-cell cryo-electron tomography (cryo-ET), cryo-focused ion beam (cryo-FIB) milling, and correlative light and electron microscopy (CLEM). Through our high-resolution cellular imaging efforts, we shine new light the physiological and pathogenic mechanisms that contribute to mitochondrial dysfunction and disease.
Education
B.S., Biology, University of Wisconsin-MadisonPh.D., Biophysics, The Scripps Research Institute
Professional Experience
2021- Present Assistant Professor, Department of Integrative Structural and Computational Biology (ISCB), Scripps Research
2019- 2021 Scripps Fellow, Department of Integrative Structural and Computational Biology (ISCB), Scripps Research
2018- 2019 Postdoctoral Researcher, Laboratory of Dr. Grant Jensen, Department of Biology, California Institute of Technology (Caltech)
2012-2013 Research Intern, Laboratory of Dr. Yevgenya Grinblat, Department of neuroscience, University of Wisconsin-Madison
2010- 2012 Associate Research Specialist, Laboratory of Dr. Francisco Pelegri, Department of Genetics and Medical Genetics, University of Wisconsin-Madison
Awards & Professional Activities
2022 Baxter Young Investigator Award, The Donald E. and Delia B. Baxter Foundation
2021 Damon Runyon-Rachleff Innovation Award, Damon Runyon Cancer Foundation
2018 Harold M. Weintraub Graduate Student Award
2015-2018 Achievement Rewards for College Scientists (ARCS) Graduate Fellowship
2014-2017 National Science Foundation (NSF) Graduate Research Fellowship
Selected References
Basanta B, Hirschi MM, Grotjahn DA, Lander, GC. A case for glycerol as an acceptable additive for single particle cryoEM samples. Acta Crystallogr D Struct Biol 2022 (PMID: 34981768)
Gardner A, Ludovic A, Fuentes D, Maritan M, Barad BA, Medina, M, Olson AJ, Grotjahn DA, Goodsell DS. CellPAINT: Turnkey illustration of molecular cell biology. Front. Bioinform 2021 (PMID: 34790910)
Basanta B, Chowdhury S, Lander GC§, Grotjahn DA§. A guided approach for subtomogram averaging of challenging macromolecular assemblies. JSBx 2020 §Corresponding authors. (PMID: 33319208)
Grotjahn, D. A., Chowdhury S, Lander, G. C. A guided approach for subtomogram averaging of challenging macromolecular assemblies (2020). bioRxiv http://dx.doi.org/10.1101/2020.02.01.930297
Grotjahn, D. A., Lander, G. C. Setting the dynein motor in motion: New insights from electron tomography Journal of Biological Chemistry 2019 294:13202-13217 DOI:10.1074/jbc.REV119.003095 PMID:31285262 PMCID:PMC6737236
Grotjahn, D. A., Chowdhury, S., Xu, Y., McKenney, R. J., Schroer, T. A., Lander, G. C. Cryo-electron tomography reveals that dynactin recruits a team of dyneins for processive motility Nature Structural & Molecular Biology 2018 25:203-+ DOI:10.1038/s41594-018-0027-7 PMID:29416113
Ge, X., Grotjahn, D., Welch, E., Lyman-Gingerich, J., Holguin, C., Dimitrova, E., Abrams, E. W., Gupta, T., Marlow, F. L., Yabe, T., Adler, A., Mullins, M. C., et al. Hecate/Grip2a acts to reorganize the cytoskeleton in the symmetry-breaking event of embryonic axis induction PLoS Genetics 2014 10 DOI:10.1371/journal.pgen.1004422 PMID:24967891 PMCID:PMC4072529