InStem develops insights into regenerative medicine studying flatworm membrane composition

Nandita Vijay, BengaluruMonday, September 4, 2017, 08:00 Hrs  [IST]

Institute for Stem Cell Biology and Regenerative Medicine (InStem), an autonomous institute of Department of Biotechnology, Bengaluru  has developed an innovative approach to deliver nucleic acids into planaria for the first time.

Planaria  is a flatworm. When a planaria is cut into tiny pieces, each piece can regenerate into an individual adult worm. It has  provided the researchers infinite possibilities to unravel the intricacies and nuances of the biology behind regeneration.

However, one major hurdle that hinders the scientists to explore the full potential of this model is their inability to deliver nucleic acids like  small antisense molecules and transgenes into this worm. So far, numerous methods such as micro-injections, gene-gun method, viral & non-viral delivery and conventional transfection approaches have been unsuccessful.

To overcome this limitation, research teams led by Dr. Dasaradhi Palakodeti and Dr. Praveen Kumar Vemula developed an understanding of the planarian cells membrane composition, to design liposomes made of cationic lipid molecules.

The researchers are Sasidharan Vidyanand, Srujan Marepally, Srishti Baid, Vairavan Lakshmanan, Nishtha Nayyar, Dhiru Bansal, Praveen Kumar Vemula, Dasaradhi Palakodeti  affiliated to inStem, while Sarah Elliott and Alejandro Sanchez Alvarado are from Stowers Institute for Medical Research and Howard Hughes Medical Institute, Kansas City, USA.

This technology according to researchers  is already paving the path towards uncovering interesting facets of the regeneration process. In one such instance, successful delivery of nucleic acids, microRNAs and anti-miRNAs has enabled the team to identify its role in regulating the fate of neural subtypes and eye progenitors.  The scientists stated that microRNA  involves  in regulating the size of the brain and the photoreceptors, during the anterior tissue regeneration in planaria. The finding is  published in the journal Development in August 2017.

“Lack of a robust transfection technology is an unmet gap which is stopping the regeneration field from expanding. This led us to team-up with Dr. Palakodeti’s group to  develop an innovative strategy to deliver nucleic acids into planarians” said Dr. Vemula, principal investigator, InStem who is also a Ramalingaswami Fellow and co-corresponding author of this work.

Use of planaria as an efficient model to study regeneration and stem cell biology has been significantly curtailed with the  absence of transgenics. This is critical for over-expression of proteins and to build fluorescent-based reporter lines that helps in tracing cells during regeneration, he added.

This work has, for the first time, highlighted the need to develop customized delivery approaches to deliver exogenous nucleic acids into planarian cells. Efforts to develop novel liposome vehicles, will aid us in the generation of transgenic planarians. To design transfection agents, a good understanding of the lipid composition of planarian cells holds the key, said Dr. Vemula.

These liposomes contain water-repelling in their structure, similar to the molecules used in soap. A systematic modulation of the liposome fluidity enabled us to efficiently deliver nucleic acids into planarian cells for the first time, said Dr. Marepally,  co-lead author.

“This is an example of a collaborative study, where specific tools were developed to address difficult problems in fundamental biology. With the help of these tools, we were able to get new insights into the role of miR-124 in the brain and visual system function” said Dr. Palakodeti, Principal Investigator, inStem, Swarnajayanti Fellow and co-corresponding author who led the study.

“Our study also emphasizes that simple and tractable model systems like planaria can be used to address many fundamental questions in the neuro-developmental biology,” said Dr. Vidyanand, a co-lead author of this work.