Manuel Diaz-Munoz is exploring the mechanisms that regulate the expression of genes involved in immune response and carcinogenesis. In particular, he is studying those involved in the production of antibodies by B cells. These mechanisms have been shown to be altered in many blood cancers and lymphomas: it is therefore essential to understand them in order to detect these cancers at an early stage, discover new therapeutic targets and develop effective vaccines.
Manuel Diaz-Munoz wants to elucidate the gene expression regulation mechanisms that control the production of proteins in B cells and, therefore, our adaptive immune response, specific to a given antigen. He is closely studying the regulations that take place at the level of RNA – intermediary molecules between genes and proteins.
In order to synthesize a protein, a gene is first transcribed into RNA, which will itself be translated into a protein. However, during this process, many mechanisms intervene at RNA level, leading to modifications in the sequence, conformation and stability of these intermediaries, with impacts on the abundance and function of the proteins ultimately produced. These mechanisms that modulate the functioning of our cells call on proteins that bind to RNA. Diaz-Munoz is seeking to understand how these interactions between proteins and RNA modulate the activation of B cells after infection, and allow the production of high-affinity antibodies that will eliminate the infectious agent. In addition, disruption of these regulatory mechanisms has been described in cancers and autoimmune diseases such as arthritis and multiple sclerosis, thereby extending the scope of his work far beyond the understanding of our defense mechanisms against infectious diseases
To learn more about the mechanisms of expression of our genes (in French):
The genome, how does it work? - educational animation - 2 min 48
To explore this theme, Diaz-Munoz has set up his own team – Post-transcriptional regulation of adaptive immune response and tumorigenesis – at the Toulouse Purpan Physiopathology Center*, with the support of the Atip-Avenir program. His career as an immunologist began at the Severo-Ochoa Molecular Biology Center in Madrid, where he studied the mechanisms of transcriptional regulation of the inflammatory response to bacterial infection and atherosclerosis. He then joined the Babraham Institute in Cambridge (UK), where he spent nine years developing his expertise in the study of RNA in lymphocytes. His work has earned him several awards and resulted in major publications, including on the post-transcriptional regulation of the immune system, B cell proliferation and the production of specific antibodies. In addition, he has shown that RNA-binding proteins are responsible for inhibiting the expression of oncogenes, such as p53, which promote cell transformation and cancer development. It is therefore very important to better understand these mechanisms in order to identify new therapeutic targets for tumor diseases.
Diaz-Munoz's work integrates animal and cellular models, and relies on the use of high-throughput sequencing and bioinformatics to obtain a global view of RNA regulation in the immune system. He has established numerous collaborations with research centers in Toulouse, Paris, Madrid, Athens and London.
*unit 1043 Inserm/CNRS/Université Toulouse 3 - Paul Sabatier