History
  Links
  Research Groups. Scientific interests and academic production since 2003
  Neuroendocrinology and Immunology
  Systems biology/Eukaryotic cell biology
  Signal Transduction
  Plant Molecular Biology
  Eukaryotic molecular biology
  Neurosciences. Chromaffin cells
  Evolutionary genetics
  Molecular and cell biology
  Neurosciences. Neuronal networks
  Neurosciences. Neurological disorders
   

 

 

 

 

 

     
  Systems biology/Eukaryotic cell biology
 
     
 

 
   
 


Group Leader
Alejandro Colman-Lerner (Investigador Adjunto CONICET)

Graduate Students
Rodrigo Baltanás (CONICET)
Lucía Durrieu (Agencia)

Undergraduate Students
Alan Bush

 
   
 


Research

Mechanisms that regulate cell fate determination

At the lab, we study the molecular basis that causes that genetically identical cells, exposed to identical environment, behave differently. We are interested in understanding the causes of the variability that “hides” behind the population mean. This is important to improve our understanding of basic processes, such as the embryo development, as well as applied issues, such as the development of new therapies to combat disease.

Cells in an organism can behave differently for a number of reasons. They might have sustained mutations or genetic rearrangements, such as those that happen to produce immunoglobulins or during oncogene amplification, or they might have differentiated into different cell types. It is also possible that cells might make different decisions by chance, due to random fluctuations in the numbers of key decision-making regulatory molecules inside cells (molecular noise). In our lab we study these last two cases, cell differentiation and the effect of noise. We use two model systems, the beer yeast S.cerevisiae and human lymphocytes in culture, and we apply a systems biology approach. In yeast, we study asymmetric division, one of the key mechanisms that results in cell type diversity. In this process, unequal segregation at the time of cell division of mRNAs, proteins or other molecules important for cell fate determination, leads to the execution of different gene expression programs. We found that a group of genes is expressed exclusively in one of the daughter cells and we then found that that is caused by the asymmetric localization of the protein that controls these genes expression, Ace2, in only one of the nuclei. We are now studying the mechanism that causes this asymmetry.

We also study mating pheromone response in yeast, which activates an evolutionary well-conserved signal transduction pathway (a G-protein coupled receptor that initiates a MAP kinase cascade). In this system, we found large cell to cell variability in the response. We determined that only a small part was due to molecular noise, while an important part was due to differences among cells in their ability to express genes. Notably, we found that the level of variability is under genetic control, by proteins that increase variability and proteins that reduce variability. We are now porting the methods and techniques we employed in yeast to the study of interferon g response in human lymphocytes (a well conserved Jak/Stat pathway).

Here we are very interested in determining if the correct control of variability in response is important to achive an appropriate immune response.

 
 


CTS1 gene promoter controlling the expression of yellow fluorescent protein (PCTS1-YFP)
in only one of the cells.

 

 

 
 


After the completion of mitosis, the Ace2-YFP protein fusion shuttles to the nucleus and remains
in only one of the cells. Numbers indicate time elapsed (in minutes) since the beginning of the observation.
CF: phase contrast; DNA: DAPI nuclear staining corresponding to time point 0.

 

Publications

  1. Gordon, A., Colman-Lerner, A., Chin, T. E., Benjamin, K. R., Yu, R. C., & Brent, R. Single-cell quantification of molecules and rates using open-source microscope-based cytometry. Nature Methods, 4 (2) 175-181.
  2. Colman-Lerner, A., Gordon, A., Pesce, C. G., Serra, E., Chin, T. E., Resnekov, O., Endy, D. & Brent, R. Regulated Cell to Cell Variation in a Cell Fate Decision System. Nature 437(7059): 699-706.
  3. Colman-Lerner, A., Chin, T. E. and Brent, R. (2001). "Yeast Cbk1 and Mob2 activate daughter-specific genetic programs to induce asymmetric cell fates." Cell 107(6): 739-750.
  4. Colman-Lerner, A. and Brent, R. (2000). Using Peptide Aptamers to Analyse the Proteome. In: New Technologies for Life Sciences: A Trends Guide Special Issue 56-60.
  5. Geyer, C. R., Colman-Lerner, A. and Brent, R. (1999). "Mutagenesis" by peptide aptamers identifies genetic network members and pathway connections." PNAS 96(15): 8567-8572.
  6. Colman-Lerner, A., Fischman, M. L., Lanuza, G. M., Bissell, D. M., Kornblihtt, A. R. and Baranao, J. L. (1999). "Evidence for a role of the alternatively spliced ED-I sequence of fibronectin during ovarian follicular development." Endocrinology 140(6): 2541-8.
  7. Lerner, A. A., Fischman, M. L., Lanuza, G., Cramer, P., Kornblihtt, A. and Baranao, J. L. (1997). "[Role of different forms of fibronectin in in vitro bovine follicular development]." Medicina (B Aires) 57(3): 332-6.
  8. Lerner, A. A., Salamone, D. F., Chiappe, M. E. and Baranao, J. L. (1995). "Comparative studies between freshly isolated and spontaneously immortalized bovine granulosa cells: protein secretion, steroid metabolism, and responsiveness to growth factors." Journal of Cellular Physiology 164(2): 395-403.
  9. Fazzini, M., Vallejo, G., Colman-Lerner, A., Trigo, R., Campo, S., Baranao, J. L. & Saragueta, P. (2006). Transforming growth factor-b1 regulates follistatin mRNA expression during in vitro bovine granulosa cell differentiation. J Cell Physiol 207(1): 40-48.
  10. Novaro, V., Pustovrh, C., Colman-Lerner, A., Radisky, D., Lo Nostro, F., Paz, D., Jawerbaum, A. and Gonzalez, E. (2002). "Nitric oxide induces gelatinase A (matrix metalloproteinase 2) during rat embryo implantation." Fertility and Sterility 78(6): 1278-87.
  11. Chiappe, M. E., Lattanzi, M. L., Colman-Lerner, A. A., Baranao, J. L. and Saragueta, P. (2002). "Expression of 3 beta-hydroxysteroid dehydrogenase in early bovine embryo development." Molecular Reproduction and Development 61(2): 135-41.
  12. Novaro, V., Colman-Lerner, A., Ortega, F. V., Jawerbaum, A., Paz, D., Lo Nostro, F., Pustovrh, C., Gimeno, M. F. and Gonzalez, E. (2001). "Regulation of metalloproteinases by nitric oxide in human trophoblast cells in culture." Reprodroduction Fertility and Development 13(5-6): 411-20.
  13. Pomata, P. E., Colman-Lerner, A. A., Baranao, J. L. and Fiszman, M. L. (2000). "In vivo evidences of early neurosteroid synthesis in the developing rat central nervous system and placenta." Brain Research, Developmental Brain Research 120(1): 83-6.
  14. Pignataro, L., Lerner, A. A., Baranao, J. L. and de Plazas, S. F. (1998). "Biosynthesis of progesterone derived neurosteroids by developing avian CNS: in vitro effects on the GABAA receptor complex." International Journal of Developmental Neuroscience 16(5): 433-41.

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