Investigating Adult Stem Cells Dynamics in the Infection Scenario.

Adult stem cells (ASCs) are fundamental players in the tissue maintenance as they serve to restore damaged tissue during injury or infection. However, during severe bacterial/ viral infections, the tissue regeneration in mammals is hugely inhibited. Recent evidence suggests that the mammalian ASCs have a limited tolerance to the infection stress. Sometimes they over-proliferate and develop cancer or they exhaust by terminally differentiation. Indeed the failure in the maintenance of healthy tissue is the cause of several deadly diseases. Hence, improving ASCs tolerance to such burden is of profound biomedical importance.

Planarian pluripotent ASCs possess extraordinary abilities to deal with such stress. The ASCs in planarians allow them to grow an entire body from a tiny tissue fragment. The genetic machinery essential for the stemness in mammalian stem cells is conserved considerably within planarian ASCs. Planarian ASCs can be easily studied in vivo or isolated by FACS in ample amount for nextgeneration sequencing applications such as RNA-Seq, ChIP-Seq etc. Hence, planarian is a convenient model system to study ASCs dynamics in vivo.

Unlike mammalian ASCs, the planarian ASCs function remains unaffected during bacterial infections. We would like to exploit this potential to investigate the molecular mechanisms governing the stem cell dynamics during chronic infections. Further, we will look to use the knowledge gained from planarian ASCs to modulate genetic machinery in mammalian ASCs to enhance their tolerance to the infection stress.

Our research program is mainly addressing the following questions:

The study will be performed on various in vivo (Planarians, Mice) and in vitro (Cell lines) model systems to address specific questions and will also involve handling of number of bacterial/ viral pathogens. We will employ wide range of Cell Biology and Molecular Genetics techniques such as RNAi, RNA-Seq, ChIP-Seq, Confocal microscopy etc. to address the above-mentioned questions.

This research will expand our understanding of how ASCs respond to infection and infection-induced tissue damage. In the long term, this will help us to design genetic strategies to increase the competence of existing as well as transplanted ASCs during regenerative therapies so that they can function efficiently under stressful chronic and acute disease conditions.

• INSPIRE Faculty Fellowship, Department of Science & Technology, February 2019, INDIA.
• Recipient of Best Poster Award in 4th European Meeting on Planarian Biology. Sep 2016, Catalunya, SPAIN.
• Best PhD Thesis in Life and Health Sciences award with the prize money of 1000 euros (~Rs. 80000), Aix-Marseille University, 2015, FRANCE.
• Infectiopole Sud fellowship for Doctoral Research, 2012, FRANCE.
• Council of Scientific & Industrial Research - Junior Research Fellowship (CSIR-JRF) 2008, INDIA.
• Department of Biotechnology - Junior Research Fellowship (DBT-JRF) 2008, INDIA.

We are looking for enthusiastic project assistants, junior research fellows and postdocs to join the group. If you are interested in our research then please feel free to contact at prasadabnave@rcb.res.in.

1. Abnave P.* and Ghigo E.*. Role of the immune system in regeneration and its dynamic interplay with adult stem cells. Seminars in Cell and Developmental Biology. 2019; 87:160-168.
2. Mihaylova Y.#, Abnave P.#, Kao D., Hughes S., Lai A., Jaber-Hijazi F., Kosaka N. and Aboobaker A.*. Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells. Nature Communications. 2018; 9(1):3633.
3. Dattani A.#, Kao D.#, Mihaylova Y., Abnave P., Hughes S., Lai A., Sahu S. and Aboobaker A.*. Epigenetic analyses of planarian stem cells demonstrate conservation of bivalent histone modifications in animal stem cells. Genome Research. 2018; 28:1-12.
4. Lai A.#, Kosaka N.#, Abnave P., Sahu S. and Aboobaker A.*. The abrogation of condensing function provides independent evidence for defining the selfrenewing population of pluripotent stem cells. Developmental Biology. 2018; 433(2):218-226.
5. Abnave P., Aboukhatwa E., Kosaka N., Thompson J., Hill M. and Aboobaker A.*. Epithelial-mesenchymal transition transcription factors control pluripotent adult stem cell migration in vivo in planarians. Development. 2017; 144(19):3440- 3453.
6. Torre C., Abnave P., Tsoumtsa L. L., Mottola G., Lepolard C., Trouplin V., Gimenez G., Desrousseaux J., Gempp S., Levasseur A., Padovani L., Lemichez E. and Ghigo E.*. Staphylococcus aureus promotes Smed-PGRP-2/Smed-setd8-1 methyltransferase signalling in planarian neoblasts to sensitize anti-bacterial gene responses during reinfection. EBioMedicine. 2017; 20:150-160.
7. Abnave P., Muracciole X. and Ghigo E.*. Macrophages in invertebrates: from insects and crustaceans to marine bivalves. Results and Problems in Cell Differentiation. 2017; 62:147–158.
8. Abnave P., Muracciole X. and Ghigo E.*. Coxiella burnetii lipopolysaccharide: what do we know? International journal of molecular sciences. 2017; 18(12):2509.
9. Abnave P., Conti F., Torre C. and Ghigo E.*. What RNAi screens in model organisms revealed about microbicidal response in mammals? Frontiers in Cellular and Infection Microbiology. 2015; 4(January):184.
10. Abnave P.#, Mottola G.#, Gimenez G., Boucherit N., Trouplin V., Torre C., Conti F., Ben Amara A., Lepolard C., Djian B., Hamaoui D., Mettouchi A., Kumar A., Pagnotta S., Bonatti S., Lepidi H., Salvetti A., Abi-Rached L., Lemichez E., Mege J. L. and Ghigo E.*. Screening in planarians identifies MORN2 as a key component in LC3- associated phagocytosis and resistance to bacterial infection. Cell Host & Microbe. 2014; 16(3):338-350.
11. Conti F., Abnave P. and Ghigo E.*. Unconventional animal models: a booster for new advances in host-pathogen interactions. Frontiers in Cellular and Infection Microbiology. 2014; 4(October):142.
12. Taware R., Abnave P., Patil D., Rajamohananan P. R., Raja R., Gowrishankar S., Kundu G. C., Kumar M., Pai K. and Ahmad A.*. Trichothecin from endophytic fungus Trichothecium sp. and its anticancer effect on murine melanoma and breast cancer cell lines. Current Biochemical Engineering. 2015; 2(1):73-80.
13. Taware R., Abnave P., Patil D., Rajamohananan P. R., Raja R., Gowrishankar S., Kundu G. C. and Ahmad A.*. Isolation, purification and characterization of Trichothecinol-A produced by endophytic fungus Trichothecium sp. and its antifungal, anticancer and antimetastatic activities. Sustainable Chemical Processes. 2014; 2(1):1-9.
14. Kumar A., Abnave P. and Ahmad A.*. Cultural, morphological and molecular characterization of vinca alkaloids producing endophytic fungus fusarium solani isolated from Catharanthus roseus. International Journal of Botany and Research. 2013; 3(2):1-12.
15. Mottola G., Boucherit N., Abnave P. and Ghigo E.*. Q fever and Coxiella burnetii: immune response and pathogenesis. Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry. 2012; 12(4):303-316.

(#equal contribution, *Corresponding author)