Deciphering the intricate process controlling platelets

A novel mechanism controlling platelet production involving suppression of ERK1/2 by DUSP1/6

BHF Intermediate Basic Science Research Fellow Dr Alexandra Mazharian is working out the intricate processes behind production of platelets - small fragments of bone marrow cells called megakaryocytes (MK cells) that circulate in the blood and plug holes in damaged blood vessels. Platelets are vital to prevent excessive bleeding after injury. But the number and behaviour of platelets is a fine balance - too few platelets can result in bleeding, whereas too many platelets can lead to blood clots, heart attacks and stroke. MK cells continuously release new platelets into the circulation, but we don’t understand what controls the number released and how they behave in terms of forming clots. Understanding how platelets are produced and what controls their activity could reveal new ways to maintain this balance. In this project, Dr Mazharian will study two families of molecules called DUSP 1/6 and ERK1/2. She will work out how these molecules work together to control MK cells and platelet production, and if DUSP 1/6 negatively controls ERK 1/2. To do this, she will use genetically modified mice, and cutting-edge cell and molecular techniques. Understanding more about the molecular processes controlling the number and behaviour of platelets in the circulation could reveal targets for new drugs to treat heart and circulatory disease.