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The Bothma group investigates how noncoding regions of the genome control gene expression in development by imaging transcription with single molecule resolution in real time.
How a single embryonic cell interprets its genome to give rise to the many diverse cell types that build an animal is one of nature’s enduring mysteries. Unravelling it promises to not only yield new insights into disorders of development and cancer, but also reveal the organizing principles of life. Even though we have uncovered all the regulatory factors and noncoding regions of the genome involved in specifying cell identity, we still don’t understand how these all come together to build an animal. One of the main reasons why this knowledge gap persisted is because until now we could not visualize a key degree of freedom – time.
Thanks to a recent series of innovations in live imaging the time is ripe for the introduction of a new paradigm in the study of embryogenesis based on how cell fates are established in living animals as development is actually taking place. We can now measure transcription factor concentration dynamics in individual cells, visualize transcription as it’s actually happening and even watch the binding of a single transcription factor molecule to DNA in a living embryo. Our experimental workhorse is the early Drosophila melanogaster embryo because of the ease of imaging and powerful genetic tools available in the system, but we are excited to expand into artificial vertebrate embryos and organoids in the future.
The goal of the group is to understand how the noncoding parts of the genome drive cell fate decisions in development, by imaging the key molecular players mediating these decisions in their endogenous context in real time. This goal is underpinned by constantly developing new ground-breaking imaging and labelling technologies that empower us to visualize these processes in ways that have never been done before. These efforts will provide deep mechanistic insights into how regulatory DNA sequence encodes biological form and function, which will pave the way for us to understand how mutations in noncoding regions of the human genome cause disease.
Birnie A,* Plat A,* Korkmaz C, Bothma JP
Download|2023
Bothma JP, Norstad MR, Alamos S and Garcia HG
Download|2018
Bothma JP,* Garcia HG,* [...] Gregor T and Levine M
Download|2015
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Bothma JP, Magliocco J and Levine M
Download|2011
Jacques Bothma begon zijn wetenschappelijke carriere in Australie, waar hij zijn Bachelor of Science in de natuurkunde behaalde aan de Universiteit van Queensland. Hij besloot vervolgens over te stappen naar biologie en een PhD project te doen in biofysica aan de Universiteit van Californië, Berkeley, in de groep van Mike Levine. Hier ontrafelde hij genetische mechanismes die zorgen voor een robuuste en gecoördineerde inzet van genexpressie tijdens de ontwikkeling. Vervolgens bleef hij in Berkeley voor zijn postdoc. Tijdens deze postdoc verrichte hij baanbrekend werk in nieuwe en kwantitatieve live-imaging benadering voor het zichtbaar maken van transcriptie en gen-regulerende netwerken in embryo’s. Dit werk deed hij in het lab van Hernan Garcia. Bothma onderzoeken hoe niet-coderende delen van het genoom genexpressie controleren tijdens de ontwikkeling en ziekte. Hij zal hiervoor de nieuwste live-imaging technieken en kwantitatieve benaderingen gebruiken.
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We are currently recruiting enthusiastic, motivated people who are interested in working on exciting problems as part of a multidisciplinary team. We are interested in applicants from a broad range of backgrounds including, but not limited to, Biophysics, Developmental Biology, Cell Biology and Physics. If you are interested in learning more about the available position(s) in the lab, please send an email to Jacques Bothma, including a CV (with grades), a cover letter and names and contact information of 3 references.
