Research Summary

Intermediate Fellowship research summary

The major drawback of stem cell research is lack of tractable and simple model system to understand stem cell function and regeneration. Recently, planarians emerged as a excellent model system to study regeneration and stem cell function. They are bilaterally symmetrical fresh water animals capable of regenerating the whole body or lost tissues and organs. They have specialized cells called neoblasts, which are functionally equivalent to mammalian stem cells. These cells are extremely sensitive to irradiation and are the only dividing cells in the animals. Genome wide RNAi screening has identified several genes essential for regeneration that are highly conserved across the animal kingdom.

The primary focus of our lab is to study post-transcriptional regulation of stem cell function and regeneration using planarian Schmidtea mediterranea as a model organism. The study involves identification and biogenesis of small RNAs and their role in planarian regeneration and stem cell function. We previously identified several microRNAs (miRNAs) in planaria and further demonstrated by deep sequencing that few of these miRNAs are specifically expressed in the neoblast populations. We are presently designing strategies to identify the targets that are regulated by neoblast specific miRNAs using both computational and experimental procedures. In addition to this, we also identified a new class of small RNAs called PIWI RNA (piRNA). We showed that piRNAs were predominantly expressed in neoblast population and are derived from the repeat elements and unique regions on the genome. Further, we have also shown the PIWI proteins, Smedwi-2 and -3 are essential for the regulation of piRNAs and knock down of these proteins lead to drastic regeneration defects. Our lab is interested to study the biogenesis and function of piRNAs in stem cell function and regeneration.

The other major project currently being undertaken by our lab is to identify RNA binding proteins and their targets essential for stem cell function and regeneration in planaria. Recently, we identified several RNA binding proteins that are specifically expressed in the neoblast population. We are presently conducting wide scale knockdown of the RNA binding proteins to identify their role in planarian regeneration and stem cell function. We are also interested to identify the targets of these RNA binding proteins, which will help us to understand the post transcriptional regulatory networks essential for stem cell function and regeneration.

References

1.Palakodeti D, Smielewska M, Lu YC, Yeo GW, Graveley BR.The PIWI proteins SMEDWI-2 & SMEDWI-3 are required for stem cell function and piRNA expression in Planarians. RNA. 2008 Jun;14(6):1174-86.

2.Palakodeti D, Smielewska M, Graveley BR. MicroRNAs from the Planarian Schmidtea mediterranea: a model system for stem cell biology. RNA. 2006 Sep;12(9):1640-9.

3.Lu YC1, Smielewska M, Palakodeti D, Lovci MT, Stefa Aigner, Yeo GW and Brenton R Graveley. Deep sequencing identifies new and regulated microRNAs in Schmidtea mediterranea. RNA 2009 Aug; 15(8): 1483-91.