Two outstanding female researchers, Prof. Alice Y. Ting and Prof. Jin Zhang, feature in the exceptional line-up of speakers brought together at the 2020 International Symposium on Chemical Biology. During their talks, they will explain how they managed to catch metabolites “in the act”.

One of the key challenges to tackle in the chemical biology field is how can we probe small molecules, metabolites and proteins directly in the cellular environment without disturbing them, so as to study their native function(s)? Developing such tools is challenging for many reasons, especially if one wants to catch these molecules “in the act”, but they can provide valuable insights into endogenous signaling mechanisms. The 2020 International Symposium on Chemical Biology organized by the NCCR Chemical Biology in Geneva will give participants the opportunity to listen to two outstanding female professors during the session “Catching them red handed”, chaired by Prof. Yimon Aye from EPFL.

Many chemical biologists are working hard to develop new tools and strategies to answer a variety of questions on the subject, including identifying target proteins of various metabolites and downstream effects of different types of modifications. Prof. Alice Y. Ting and Prof. Jin Zhang have both been working for many years in the field, and the 2020 International Symposium on Chemical Biology is the best occasion to hear them present their research.

After a PhD in Chemistry at UC Berkeley and a postdoc with Nobel Prize winner Roger Y. Tsien at UCSD, Prof. Alice Y. Ting started her independent career at MIT in 2002 and moved to Stanford University in 2016. In 2018, she received the NIH Director’s transformative research award. By combining synthetic organic chemistry and directed evolution methods in her lab, she was able to develop powerful tools for precise proteomic mapping in living cells. She developed an enzyme-based proximity labeling method with the engineered enzyme APEX2, which uses a small molecule as a substrate to biotinylate any endogenous protein in its vicinity (1-10 nm away). Biotinylated proteins can then be harvested and identified by mass spectrometry. Prof. Alice Y. Ting and her team used this strategy to map proteins in neuronal synaptic clefts and in the mitochondria, and other groups applied the technology in various contexts, including in C. elegans and D. melanogaster. She also developed several tools for high-resolutions imaging of individual proteins in cells, including targetable quantum dots.

Prof. Jin Zhang received her PhD in Chemistry from the University of Chicago in 2000 before moving to UCSD for her postdoctoral research with Nobel Prize winner Roger Y. Tsien. She then started her lab at Johns Hopkins University School of Medicine in 2003 and moved back to UCSD as full professor in 2015. She was recently selected for the 2019 ICBS Global lectureship. Her research focuses on understanding how cellular signaling events are spatiotemporally regulated in various contexts. With her team, she developed fluorescent activity biosensors for specific kinases, including Protein Kinase A, PI3K or MAPK, phosphatases and metabolites. She uses these sensors in super-resolution imaging to investigate regulatory pathways involving these enzymes. Using a combination of chemistry, pure biochemistry and computational approaches, Prof. Jin Zhang was able to uncover an oscillatory circuit involving calcium in insulin-secreting β cells and come up with a precise model for PKA nuclear signaling. She is now focusing on mapping the “activity architecture” of the cell by investigating the spatial organization of various bioactive molecules and enzymes in healthy and cancer cells.

The talk of Prof. Alice Y. Ting, called “Chemogenetic and optogenetic technologies for probing molecular and cellular interactions”, will highlight novel direct evolution approaches for protein engineering. Prof. Jin Zhang’s talk entitled “Illuminating the biochemical activity architecture of the cell” will introduce a series of fluorescent biosensors and their use to probe the compartmentalized signaling activities.