Deciphering BMP6 regulatory mechanisms using CRISPR/Cas9-based screening approach

nsc

Project number: 2015/19/P/NZ2/03278

Project title: “"Deciphering BMP6 regulatory mechanisms using CRISPR/Cas9-based screening approach”

Project leader: dr. Katarzyna Mleczko-Sanecka

Source of funding: National Science Centre, Poland

Budget: 893 104 PLN

Project Duration: 01.01.2017-31.12.2018

About the project:
Maintenance of an appropriate iron balance is essential for the correct functioning of the organism, and thus an increasing knowledge of the genetic control of iron homeostasis is important for human health. To prevent iron-overload diseases, excessive iron levels must be correctly sensed to stimulate expression of the iron-regulatory hormone hepcidin that limits further iron absorption from the diet. The objective of our work is to better understand the process of iron-sensing in the liver. We are seeking to identify still elusive mechanisms that control iron-triggered induction of bone morphogenetic protein 6 (BMP6), a key iron-sensing cytokine produced by the liver sinusoidal endothelial cells (LSECs) that stimulates hepcidin production.  Our preliminary data suggest that a factor secreted by iron-loaded hepatocytes rather than iron deposition in LSECs serves as a signal to enhance endothelial BMP6 expression. Using cell lines and primary liver cell cultures, we are now characterizing one candidate protein that may mediate communication between iron-laden hepatocytes and LSECs. We expect that our work which will shed light on a novel iron-sensing mechanism in the liver, that leads to induction of the BMP6-hepcidin axis. 

Publications:
Mleczko-Sanecka K, da Silva AR, Call D, Neves J, Schmeer N, Damm G, Seehofer D and Muckenthaler MU. Imatinib and spironolactone suppress hepcidin expression Haematologica. 2017 Jul;102(7):1173-1184.

Posters at the international conferences:
Poster at the Seventh Congress of the International BioIron Society (IBIS) Biennial World Meeting (BioIron 2017), May 7 – 11, 2017, UCLA, Los Angeles, USA. IMATINIB AND SPIRONOLACTONE SUPPRESS HEPCIDIN EXPRESSION. Katarzyna Mleczko-Sanecka, Debora Call, Ana Rita da Silva, Nikolai Schmeer, Melanie Kiessig, Georg Damm and Martina Muckenthaler. Presented By: Katarzyna Mleczko-Sanecka, PhD


eu flagThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 665778