Dr James Krycer

NHMRC Early Career Fellow
School of Life and Environmental Sciences

D17 - Charles Perkins Centre
The University of Sydney


Research interests

I am interested in how cells balance nutrient supply with energetic demand. For instance, muscle cells switch between creatine phosphate, glucose, glycogen, and fat during exericse. Adipocytes (fat cells) switch from lipid storage after a meal to lipid release during fasting. Cancer cells prefer to ferment glucose, even in the presence of oxygen. How does a cell fine-tune its response to such fluctuating nutrient and hormonal milleau?

I address this question using insulin signalling as my primary research focus. It is well-known that after a meal, insulin stimulates particular cells to take up glucose. My work with Prof. David James is expanding this classic paradigm by exploring two exciting findings:

1) Insulin causes the modification (phosphorylation) of hundreds of metabolic proteins. This could mean that insulin (and kinase signalling) plays a much larger role in coordinating cell metabolism beyond just glucose uptake. What other roles could insulin signalling have in processing glucose and other nutrients (e.g. amino acids)? How does this go awry in pre-diabetes?

2) Upon entering the cell, glucose can be processed in many ways: e.g., CO2, lactate, lipid. We have found that the specific fate of glucose can actually influence how cells subsequently respond to insulin. This means that not only does signalling control metabolism, but metabolism can in turn regulate signalling. What is the molecular mechanism by which this occurs? Could this explain how insulin resistance occurs?

To explore these two areas, I study how cellular signalling and metabolism interact at the molecular level, using a combination of molecular, biochemical, and 'omics (metabolomic, proteomic) techniques in cell culture and animal models. Deciphering these interactions has important implications for insulin resistance (nutrient oversupply) and cancer (hyperactive signalling).

Selected grants

2014

  • Matching supply and demand: how does metabolism fine-tune signal transduction; Krycer J; National Health and Medical Research Council (NHMRC)/Early Career Fellowships.

Selected publications

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Journals

  • Norris, D., Yang, P., Krycer, J., Fazakerley, D., James, D., Burchfield, J. (2017). An improved Akt reporter reveals intra- and inter-cellular heterogeneity and oscillations in signal transduction. Journal of Cell Science, 130, 2757-2766. [More Information]
  • Krycer, J., Fisher-Wellman, K., Fazakerley, D., Muoio, D., James, D. (2017). Bicarbonate alters cellular responses in respiration assays. Biochemical and Biophysical Research Communications, 489, 399-403. [More Information]
  • Krycer, J., Fazakerley, D., Cater, R., Thomas, K., Naghiloo, S., Burchfield, J., Humphrey, S., Vandenberg, R., Ryan, R., James, D. (2017). The amino acid transporter SLC1A3 is plasma membrane-localised in adipocytes and its activity is insensitive to insulin. FEBS Letters, 591(2), 322-330. [More Information]
  • Schoenwaelder, S., Darbousset, R., Cranmer, S., Ramshaw, H., Orive, S., Sturgeon, S., Yuan, Y., Yao, Y., Krycer, J., Woodcock, J., Maclean, J., James, D., Jackson, S., et al (2016). 14-3-3z regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function. Nature Communications, 7, 1-15. [More Information]
  • Solon-Biet, S., Cogger, V., Pulpitel, T., Heblinski, M., Wahl, D., McMahon, A., Warren, A., Durrant-Whyte, J., Walters, K., Krycer, J., Ponton, F., Gokarn, R., Wali, J., Conigrave, A., James, D., Raubenheimer, D., Le Couteur, D., Simpson, S., et al (2016). Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework. Cell Metabolism, 24(4), 555-565. [More Information]
  • Kleinert, M., Parker, B., Chaudhuri, R., Fazakerley, D., Serup, A., Thomas, K., Krycer, J., Sylow Hansen, L., Fritzen, A., Hoffman, N., James, D., et al (2016). mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3. Molecular Metabolism, 5(8), 646-655. [More Information]
  • Vafaee, F., Krycer, J., Ma, X., Burykin, T., James, D., Kuncic, Z. (2016). ORTI: An Open-Access Repository of Transcriptional Interactions for Interrogating Mammalian Gene Expression Data. PloS One, 11(10), 1-21. [More Information]
  • Domanova, W., Krycer, J., Chaudhuri, R., Yang, P., Vafaee, F., Fazakerley, D., Humphrey, S., James, D., Kuncic, Z. (2016). Unraveling Kinase Activation Dynamics Using Kinase-Substrate Relationships from Temporal Large-Scale Phosphoproteomics Studies. PloS One, 11(6), 1-14. [More Information]
  • Wong, M., Krycer, J., Burchfield, J., James, D., Kuncic, Z. (2015). A generalised enzyme kinetic model for predicting the behaviour of complex biochemical systems. FEBS Open Bio, 5, 226-239. [More Information]
  • Trefely, S., Khoo, P., Krycer, J., Chaudhuri, R., Fazakerley, D., Parker, B., Sultani, G., Lee, J., Stephan, J., Torres, E., James, D., Stoeckli, J., et al (2015). Kinome Screen Identifies PFKFB3 and Glucose Metabolism as Important Regulators of the Insulin/IGF-1 Signalling Pathway. The Journal of Biological Chemistry, 290(43), 25834-25846. [More Information]
  • Fazakerley, D., Naghiloo, S., Chaudhuri, R., Koumanov, F., Burchfield, J., Thomas, K., Krycer, J., Prior, M., Parker, B., Murrow, B., Stoeckli, J., Meoli, C., James, D., et al (2015). Proteomic Analysis of GLUT4 Storage Vesicles Reveals Tumour Suppressor Candidate 5 (TUSC5) as a Novel Regulator of Insulin Action in Adipocytes. The Journal of Biological Chemistry, 290(39), 23528-23542. [More Information]
  • Ma, D., Stolte, C., Krycer, J., James, D., O'Donoghue, S. (2015). SnapShot: Insulin/IGF1 Signaling. Cell, 161(4), 948-948. [More Information]
  • Kleinert, M., Sylow Hansen, L., Fazakerley, D., Krycer, J., Thomas, K., Oxbøll, A., Jordy, A., Jensen, T., Yang, G., Schjerling, P., James, D., et al (2014). Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo. Molecular Metabolism, 3(6), 630-641. [More Information]
  • Fletcher, R., Gribben, C., Ma, X., Burchfield, J., Thomas, K., Krycer, J., James, D., Fazakerley, D. (2014). The Role of the Niemann-Pick Disease, Type C1 Protein in Adipocyte Insulin Action. PloS One, 9(4), 1-10. [More Information]

2017

  • Norris, D., Yang, P., Krycer, J., Fazakerley, D., James, D., Burchfield, J. (2017). An improved Akt reporter reveals intra- and inter-cellular heterogeneity and oscillations in signal transduction. Journal of Cell Science, 130, 2757-2766. [More Information]
  • Krycer, J., Fisher-Wellman, K., Fazakerley, D., Muoio, D., James, D. (2017). Bicarbonate alters cellular responses in respiration assays. Biochemical and Biophysical Research Communications, 489, 399-403. [More Information]
  • Krycer, J., Fazakerley, D., Cater, R., Thomas, K., Naghiloo, S., Burchfield, J., Humphrey, S., Vandenberg, R., Ryan, R., James, D. (2017). The amino acid transporter SLC1A3 is plasma membrane-localised in adipocytes and its activity is insensitive to insulin. FEBS Letters, 591(2), 322-330. [More Information]

2016

  • Schoenwaelder, S., Darbousset, R., Cranmer, S., Ramshaw, H., Orive, S., Sturgeon, S., Yuan, Y., Yao, Y., Krycer, J., Woodcock, J., Maclean, J., James, D., Jackson, S., et al (2016). 14-3-3z regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function. Nature Communications, 7, 1-15. [More Information]
  • Solon-Biet, S., Cogger, V., Pulpitel, T., Heblinski, M., Wahl, D., McMahon, A., Warren, A., Durrant-Whyte, J., Walters, K., Krycer, J., Ponton, F., Gokarn, R., Wali, J., Conigrave, A., James, D., Raubenheimer, D., Le Couteur, D., Simpson, S., et al (2016). Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework. Cell Metabolism, 24(4), 555-565. [More Information]
  • Kleinert, M., Parker, B., Chaudhuri, R., Fazakerley, D., Serup, A., Thomas, K., Krycer, J., Sylow Hansen, L., Fritzen, A., Hoffman, N., James, D., et al (2016). mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3. Molecular Metabolism, 5(8), 646-655. [More Information]
  • Vafaee, F., Krycer, J., Ma, X., Burykin, T., James, D., Kuncic, Z. (2016). ORTI: An Open-Access Repository of Transcriptional Interactions for Interrogating Mammalian Gene Expression Data. PloS One, 11(10), 1-21. [More Information]
  • Domanova, W., Krycer, J., Chaudhuri, R., Yang, P., Vafaee, F., Fazakerley, D., Humphrey, S., James, D., Kuncic, Z. (2016). Unraveling Kinase Activation Dynamics Using Kinase-Substrate Relationships from Temporal Large-Scale Phosphoproteomics Studies. PloS One, 11(6), 1-14. [More Information]

2015

  • Wong, M., Krycer, J., Burchfield, J., James, D., Kuncic, Z. (2015). A generalised enzyme kinetic model for predicting the behaviour of complex biochemical systems. FEBS Open Bio, 5, 226-239. [More Information]
  • Trefely, S., Khoo, P., Krycer, J., Chaudhuri, R., Fazakerley, D., Parker, B., Sultani, G., Lee, J., Stephan, J., Torres, E., James, D., Stoeckli, J., et al (2015). Kinome Screen Identifies PFKFB3 and Glucose Metabolism as Important Regulators of the Insulin/IGF-1 Signalling Pathway. The Journal of Biological Chemistry, 290(43), 25834-25846. [More Information]
  • Fazakerley, D., Naghiloo, S., Chaudhuri, R., Koumanov, F., Burchfield, J., Thomas, K., Krycer, J., Prior, M., Parker, B., Murrow, B., Stoeckli, J., Meoli, C., James, D., et al (2015). Proteomic Analysis of GLUT4 Storage Vesicles Reveals Tumour Suppressor Candidate 5 (TUSC5) as a Novel Regulator of Insulin Action in Adipocytes. The Journal of Biological Chemistry, 290(39), 23528-23542. [More Information]
  • Ma, D., Stolte, C., Krycer, J., James, D., O'Donoghue, S. (2015). SnapShot: Insulin/IGF1 Signaling. Cell, 161(4), 948-948. [More Information]

2014

  • Kleinert, M., Sylow Hansen, L., Fazakerley, D., Krycer, J., Thomas, K., Oxbøll, A., Jordy, A., Jensen, T., Yang, G., Schjerling, P., James, D., et al (2014). Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo. Molecular Metabolism, 3(6), 630-641. [More Information]
  • Fletcher, R., Gribben, C., Ma, X., Burchfield, J., Thomas, K., Krycer, J., James, D., Fazakerley, D. (2014). The Role of the Niemann-Pick Disease, Type C1 Protein in Adipocyte Insulin Action. PloS One, 9(4), 1-10. [More Information]

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