Life Sciences & Biotechnology
Title : | In vitro and in vivo investigation of biomolecular condensate formation by HOX and TALE transcription factors and their role in leukemia |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Protein biochemistry |
Principal Investigator : | Dr. srijeeb Karmakar, Indian Institute of Technology (IIT) Kharagpur, West Bengal |
Timeline Start Year : | 2024 |
Timeline End Year : | 2026 |
Contact info : | srijibkarmakar@gmail.com |
Details
Executive Summary : | Hox transcription factors are essential for the development of bilateral vertebrates and hematopoietic stem cells. Deregulated Hox function is linked to leukemia, with HOXA9 being the most highly correlated gene for poor prognosis in acute myeloid leukemia. HOXA genes are dysregulated in T-cell acute lymphocytic leukemia and upregulated in mixed-lineage leukemia and T-cell acute lymphoblastic leukemia cases, suggesting oncogenic roles. HOXB4 can increase self-renewal of hematopoietic stem cells without disrupting normal differentiation. Hox genes are important targets for therapy of leukemia due to their role in hematopoiesis and leukemogenesis.
There are 39 Hox genes in humans, located in four chromosomes and consisting of a 60 amino acid DNA-binding domain called the homeodomain. Intrinsically disordered regions (IDRs) regulate transcription factors' function via post-translational modifications, interactions with other proteins, and auto-inhibition. Hox proteins often partner with the TALE family of transcription factors, but their interactions are weak in vitro. The hypothesis is that disordered regions in some Hox and TALE proteins promote liquid-liquid phase separation and help form biomolecular condensates in the cell, facilitating interactions and functional partnerships. |
Total Budget (INR): | |
Organizations involved