Academic Appointments

Honors & Awards

  • Young Investigator Award, Air Force Office of Scientific Research (2010)
  • Graduate Course Teaching Award, University of California, San Francisco (2006)

Professional Education

  • Ph.D., Univ. California, San Francisco, Molecular Biology and Genetics (2009)
  • B.S., Mass. Institute of Technology, Aerospace Engineering (2004)

Research & Scholarship

Current Research and Scholarly Interests

The over-arching aim of our lab is to transform our understanding of plant photosynthesis by developing game-changing tools. In the long run, we aim to contribute to increasing crop yields by engineering photosynthesis.

Photosynthesis provides fixed carbon and energy for nearly all life on Earth. Yet we know very little about many key aspects of this fascinating process. What is the full set of genes required for photosynthesis? Which parts work together? What do all the uncharacterized parts do?
Photosynthetic cells have the capacity to harness light energy with incredible efficiency- but if not managed properly, full sunlight can fry the photosynthetic apparatus. How is photosynthesis regulated in response to a varying environment?
Rubisco, the key carbon-fixing enzyme in photosynthesis, is remarkably slow (3 carbon-fixation reactions per second per enzyme). This slowness limits the growth of many crops- yet some organisms have found solutions. How can we overcome these limitations to accelerate photosynthetic growth?

In our first three years, we have focused on developing tools to enable high-throughput genotyping and phenotyping of mutants in the single-celled green alga Chlamydomonas. In our view, there is a burning need for a powerful single-celled model organism for plant functions. The dream is that if we could adapt high-throughput genetics tools from yeast to Chlamydomonas, we could characterize the functions of many conserved genes much more rapidly than we currently can with multi-cellular plant models.

In addition to the high-throughput work, we are also working on in-depth characterization of several specific genes with functions in photosynthesis and plant lipid biology.


2014-15 Courses

Graduate and Fellowship Programs

  • Biology (School of Humanities and Sciences) (Phd Program)


Journal Articles

  • A fluorescence-activated cell sorting-based strategy for rapid isolation of high-lipid Chlamydomonas mutants. Plant journal Terashima, M., Freeman, E. S., Jinkerson, R. E., Jonikas, M. C. 2015; 81 (1): 147-159


    There is significant interest in farming algae for the direct production of biofuels and valuable lipids. Chlamydomonas reinhardtii is the leading model system for studying lipid metabolism in green algae, but current methods for isolating mutants with perturbed lipid content in this organism are slow and tedious. Here, we present the Chlamydomonas High Lipid Sorting (CHiLiS) strategy, which enables enrichment of high-lipid mutants by fluorescence-activated cell sorting (FACS) of pooled mutants stained with the lipid-sensitive dye Nile Red. This method only takes five weeks from mutagenesis to mutant isolation. We developed a staining protocol that allows quantitation of lipid content while preserving cell viability. We improved separation of high-lipid mutants from wild-type by using each cell's chlorophyll fluorescence as an internal control. We initially demonstrated 20-fold enrichment of the known high-lipid mutant sta1 from a mixture of sta1 and wild-type cells. We then applied CHiLiS to sort thousands of high-lipid cells from a pool of ~60,000 mutants. Flow cytometry analysis of 24 individual mutants isolated by this approach revealed that ~50% showed a reproducible high lipid phenotype. We further characterized 9 of the mutants with highest lipid content by flame ionization detection and mass spectrometry lipidomics. All mutants analyzed had higher triacylglycerol content and perturbed whole-cell fatty-acid composition. One arbitrarily chosen mutant was evaluated by microscopy, revealing larger lipid droplets than wild-type. The unprecedented throughput of CHiLiS opens the door to a systems-level understanding of green algal lipid biology by enabling genome-saturating isolation of mutants in key genes. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/tpj.12682

    View details for PubMedID 25267488

  • High-Throughput Genotyping of Green Algal Mutants Reveals Random Distribution of Mutagenic Insertion Sites and Endonucleolytic Cleavage of Transforming DNA PLANT CELL Zhang, R., Patena, W., Armbruster, U., Gang, S. S., Blum, S. R., Jonikas, M. C. 2014; 26 (4): 1398-1409
  • Comprehensive Characterization of Genes Required for Protein Folding in the Endoplasmic Reticulum SCIENCE Jonikas, M. C., Collins, S. R., Denic, V., Oh, E., Quan, E. M., Schmid, V., Weibezahn, J., Schwappach, B., Walter, P., Weissman, J. S., Schuldiner, M. 2009; 323 (5922): 1693-1697


    Protein folding in the endoplasmic reticulum is a complex process whose malfunction is implicated in disease and aging. By using the cell's endogenous sensor (the unfolded protein response), we identified several hundred yeast genes with roles in endoplasmic reticulum folding and systematically characterized their functional interdependencies by measuring unfolded protein response levels in double mutants. This strategy revealed multiple conserved factors critical for endoplasmic reticulum folding, including an intimate dependence on the later secretory pathway, a previously uncharacterized six-protein transmembrane complex, and a co-chaperone complex that delivers tail-anchored proteins to their membrane insertion machinery. The use of a quantitative reporter in a comprehensive screen followed by systematic analysis of genetic dependencies should be broadly applicable to functional dissection of complex cellular processes from yeast to human.

    View details for DOI 10.1126/science.1167983

    View details for Web of Science ID 000264559800030

    View details for PubMedID 19325107

  • Actin Is Required for IFT Regulation in Chlamydomonas reinhardtii CURRENT BIOLOGY Avasthi, P., Onishi, M., Karpiak, J., Yamamoto, R., Mackinder, L., Jonikas, M. C., Sale, W. S., Shoichet, B., Pringle, J. R., Marshall, W. F. 2014; 24 (17): 2025-2032
  • J Domain Co-chaperone Specificity Defines the Role of BiP during Protein Translocation JOURNAL OF BIOLOGICAL CHEMISTRY Vembar, S. S., Jonikas, M. C., Hendershot, L. M., Weissman, J. S., Brodsky, J. L. 2010; 285 (29): 22484-22494


    Hsp70 chaperones can potentially interact with one of several J domain-containing Hsp40 co-chaperones to regulate distinct cellular processes. However, features within Hsp70s that determine Hsp40 specificity are undefined. To investigate this question, we introduced mutations into the ER-lumenal Hsp70, BiP/Kar2p, and found that an R217A substitution in the J domain-interacting surface of BiP compromised the physical and functional interaction with Sec63p, an Hsp40 required for ER translocation. In contrast, interaction with Jem1p, an Hsp40 required for ER-associated degradation, was unaffected. Moreover, yeast expressing R217A BiP exhibited defects in translocation but not in ER-associated degradation. Finally, the genetic interactions of the R217A BiP mutant were found to correlate with those of known translocation mutants. Together, our results indicate that residues within the Hsp70 J domain-interacting surface help confer Hsp40 specificity, in turn influencing distinct chaperone-mediated cellular activities.

    View details for DOI 10.1074/jbc.M110.102186

    View details for Web of Science ID 000279702200060

    View details for PubMedID 20430885

  • Automated identification of pathways from quantitative genetic interaction data MOLECULAR SYSTEMS BIOLOGY Battle, A., Jonikas, M. C., Walter, P., Weissman, J. S., Koller, D. 2010; 6


    High-throughput quantitative genetic interaction (GI) measurements provide detailed information regarding the structure of the underlying biological pathways by reporting on functional dependencies between genes. However, the analytical tools for fully exploiting such information lag behind the ability to collect these data. We present a novel Bayesian learning method that uses quantitative phenotypes of double knockout organisms to automatically reconstruct detailed pathway structures. We applied our method to a recent data set that measures GIs for endoplasmic reticulum (ER) genes, using the unfolded protein response as a quantitative phenotype. The results provided reconstructions of known functional pathways including N-linked glycosylation and ER-associated protein degradation. It also contained novel relationships, such as the placement of SGT2 in the tail-anchored biogenesis pathway, a finding that we experimentally validated. Our approach should be readily applicable to the next generation of quantitative GI data sets, as assays become available for additional phenotypes and eventually higher-level organisms.

    View details for DOI 10.1038/msb.2010.27

    View details for Web of Science ID 000279636000003

    View details for PubMedID 20531408

  • Identification of yeast proteins necessary for cell-surface function of a potassium channel PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Haass, F. A., Jonikas, M., Walter, P., Weissman, J. S., Jan, Y., Jan, L. Y., Schuldiner, M. 2007; 104 (46): 18079-18084


    Inwardly rectifying potassium (Kir) channels form gates in the cell membrane that regulate the flow of K(+) ions into and out of the cell, thereby influencing the membrane potential and electrical signaling of many cell types, including neurons and cardiomyocytes. Kir-channel function depends on other cellular proteins that aid in the folding of channel subunits, assembly into tetrameric complexes, trafficking of quality-controlled channels to the plasma membrane, and regulation of channel activity at the cell surface. We used the yeast Saccharomyces cerevisiae as a model system to identify proteins necessary for the functional expression of a mammalian Kir channel at the cell surface. A screen of 376 yeast strains, each lacking one nonessential protein localized to the early secretory pathway, identified seven deletion strains in which functional expression of the Kir channel at the plasma membrane was impaired. Six deletions were of genes with known functions in trafficking and lipid biosynthesis (sur4Delta, csg2Delta, erv14Delta, emp24Delta, erv25Delta, and bst1Delta), and one deletion was of an uncharacterized gene (yil039wDelta). We provide genetic and functional evidence that Yil039wp, a conserved, phosphoesterase domain-containing protein, which we named "trafficking of Emp24p/Erv25p-dependent cargo disrupted 1" (Ted1p), acts together with Emp24p/Erv25p in cargo exit from the endoplasmic reticulum (ER). The seven yeast proteins identified in our screen likely impact Kir-channel functional expression at the level of vesicle budding from the ER and/or the local lipid environment at the plasma membrane.

    View details for DOI 10.1073/pnas.0708765104

    View details for Web of Science ID 000251077000034

    View details for PubMedID 17989219

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