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Exploring microbiome function

Dr. Shalev Itzkovitz, of the Department of Molecular Cell Biology, has combined RNA sequencing, computational and experimental tools, and advanced single-molecule imaging techniques to uncover interactions among cells, and between cells and the microbiome. Concentrating on the epithelium, the layer of elongated cells that line the intestines, he has discovered that the two sides of the cell differ in the composition of their mRNA and produce different complements of proteins.

Moreover, he found that the number of ribosomes—cellular organelles where proteins are produced—is much higher on the side of the epithelial cells that faces the interior of the gut. The work of Dr. Itzkovitz and his team is helping to clarify how bacteria in the microbiome interact with specialized cell populations and the proteins they produce, thereby enabling the efficient processing of food and the absorption of nutrients.

The Personalized Nutrition Project

Prof. Eran Segal of the Department of Computer Science and Applied Mathematics, and Prof. Eran Elinav, a member of the Department of Immunology and a medical doctor, are collaborating on a large-scale study of how foods affect the microbiota of different individuals.

Human volunteers are equipped with devices that monitored the rise and fall of their blood sugar throughout the day, over a seven-day period. Based on the data gathered, the scientists have developed algorithms for predicting the response of each individual’s microbiota to a wide variety of foods, and have also generated the world’s first science-based, personalized diets based on each individual’s microbiome data.

The microbiome in Multiple Sclerosis

Prof. Eran Segal of the Department of Computer Science and Applied Mathematics, and Prof. Eran Elinav of the Department of Immunology have launched a long-term — together with clinical partners at Sheba Medical Center — are tracking newly diagnosed multiple sclerosis (MS) patients and monitoring the progression of the disease along with changes in the patient’s microbiome. They are pursuing a multi-pronged approach to decipher the role of the microbiota in MS, by developing microbiome-based machine learning algorithms aimed at distinguishing healthy individuals from MS patients, and predicting the annual rate of disease progression. From there, they hope to identify the microbiome signatures that characterize the relapse state; and identify potential targets for future treatment.

The microbiome’s daily rhythms

Prof. Eran Segal and Prof. Eran Elinav, working with clinicians at the Tel Aviv Sourasky Medical Center, have demonstrated that both mice and humans with disrupted daily wake-sleep patterns, and impaired feeding rhythms, exhibit changes in the composition and function of their gut bacteria, thereby increasing their risk for obesity and glucose intolerance. 

The tumor microbiome

Resistance to chemotherapy in advanced cancer patients is widespread despite a surge in new anticancer drugs. While most cancer research focuses on the abnormal dynamics of the cancer cell, Dr. Ravid Straussman in the Department of Molecular Cell Biology has demonstrated that the majority of human pancreatic tumors contain bacteria and that, in many cases, these bacteria can degrade the anti-cancer drug gemcitabine into an inactive metabolite.

The Straussman group has developed multiple methods to better detect, characterize and visualize bacteria in human tumors and have expanded their research to take in the effect of not only the tumor microbiome, but the role of the gut microbiome as well, on resistance to drugs and immunotherapy for cancer.

Microbiome, acquired immunity, and cancer

Prof. Eran Elinav was the first to describe the inflammasome, a multi-protein complex found in cells which recognizes bacterial and viral antigens and can initiate a rapid immune response. Recently, he showed that inflammasomes, as critical sensors of metabolic perturbations in gut and other parts of the body, also play a role in cancer progression. Working together with Prof. Eran Segal, Prof. Elinav is in process of developing a highly sensitive and specific method for the early detection of colorectal cancer using stool samples. This method will enable early detection, follow up and in the future potential microbiome-targeting treatment that may be added to the armament of anti-cancer drugs.

Genomic approach to microbiome analysis

Prof. Rotem Sorek of the Department of Molecular Genetics is using genomic and large-scale DNA sequencing techniques to better understand the ecology and biology of microbes— especially the astounding 99% of bacteria that cannot be grown in laboratory conditions.

His computational methods have produced key insights about how microbes exchange genetic material, generate bacteria-killing peptides, and acquire immunity to viruses and other threats. His findings may inform future strategies for battling the important biomedical challenge of antibiotic resistance.