Dr. Tomer Kalisky – Revealing the Secrets of Biological Systems

When Tomer Kalisky was a graduate student in physics, he used statistical tools to advance the theory of network optimization. But after completing his PhD – under BIU’s Prof. Shlomo Havlin – Kalisky decided to cross over into the experimental sciences. Today, he is applying his theoretical training to unlocking the optimization secrets of biological systems.

 

“With so many interconnected factors involved, and so many different levels of activity, studies combining both computation and experiment are an important avenue for revealing how biological systems work,” Kalisky says. “What makes this interesting – besides the fact that there’s a lot of room for discovery – is that my training in complex networks allows me to approach the big questions of biology, using the tools of physics.”

 

A recently-recruited scientist with appointments both at BINA and the Faculty of Engineering, Kalisky did post-doctoral research at the Weizmann Institute and Stanford University, before returning to Israel in 2013. Specializing in single-cell genomics as it relates to the study of stem cells, tissue regeneration and cancer, Kalisky says that the wide-ranging training he received from his various mentors gave him the tools – and the attitude – needed to move forward as head of his own independent lab.

 

“My supervisor at Weizmann, Prof. Uri Alon – an expert in the analysis of biological networks – introduced me to systems biology and inspired me with his original and creative approach. At Stanford, Prof. Stephen Quake – a bioengineer who developed ground-breaking technologies for precision measurements – urged me to pursue big and ambitious projects using high throughput technologies,” Kalisky recalls, adding that he continues to collaborate with his former mentors, as well as clinical experts in stem cell biology and cancer. “I use genomic technologies to bridge the gap between what’s going on inside a single cell, and the overall cell-population dynamics characteristic of normal and diseased tissues.”

 

In his experimental set-up, Kalisky relies on a palm-size microfluidic platform invented by Quake, his Stanford advisor. “Microfluidics can be described as the biological equivalent of the integrated circuit,” Kalisky says, explaining that each “chip” is etched with  thousands of micromechanical channels that allow specific biological agents to be loaded and mixed with each other in many different combinations. “Microfluidics allows us to perform ten thousand PCR reactions in parallel. By examining the levels of amplified, double-stranded DNA produced from single cells in these reactions – levels that can be quantified using fluorescent microscopy – we get an overview of the small-component dynamics that, together, create the bigger biological picture.”

 

Kalisky’s experiments focus on identifying the various types of cells found in heterogeneous tissue by characterizing cells’ transcriptional profiles. Measuring how much of each gene is expressed in hundreds of individual cells, Kalisky “dissects” tissues into discrete groups of cells that share both common profiles and – significantly for medicine – common biological function. “If you wanted to improve chemotherapy, it would be important to target cells that have a tendency toward self-renewal of the tumor, rather than rapid division – something that can be revealed by comparing their gene expression activity,” Kalisky says. “It might also be possible to use this type of genomic data to identify markers for early cancer detection, or to predict a patient’s prognosis.”

 

Kalisky is also using microfluidics to reveal new data relevant to stem cell biology. “All complex biological systems – whether it’s a developing embryo, a regenerating tissue, or a tumor – are composed of heterogeneous cell types, and single cell genomics allows us to characterize these cell types independently, and show how they interact,” he says.

Currently collaborating with a number of Bar-Ilan colleagues, Kalisky also works in close proximity to his wife Dr. Beena Kalisky, who joined the BINA faculty in 2013. “Work-family balance is very important,” says this father of three. “As a scientist, my goal is to continue to use genomic technologies to get a clearer, quantitative picture of how tissues develop, and how they function in both health and disease. As a parent, my goal is to do what we’re already doing – raising our children here in Israel.”

 

For more on Dr. Kalisky click here.