Danielle Grotjahn, PhD

Scripps Fellow
Department of Integrative Structural and Computational Biology
California Campus


 Email

Scripps Research Joint Appointments

Faculty, Graduate Program

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-Madison, 2010
Ph.D., Biophysics, The Scripps Research Institute, 2018

Professional Experience

2019- Present  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

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

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