Read more at the Mitchell lab website

Overview

Our lab studies how cells decode, respond, and adapt to external stimuli in the context of multi-lateral host-drug-microbiome interactions such as in the tumor-microbiome. We address this complexity challenge by reconstituting multi-member systems with varying levels of complexity from individual parts that are well-understood on their own (model organisms, clonal cell-lines, drugs, and metabolites). This bottom-up approach allows us to investigate the unique properties that emerge in complex systems using tractable host-drug-microbiome models. Our experimental work leverages on genomics, transcriptomics, and quantitative high-throughput microscopy and is complemented by computational approaches and mathematical modeling.

Bacteria-drug interactions

The human gut microbiome is a central factor influencing the efficacy of host-targeted drugs. This impact is facilitated by a myriad of complex host-drug-microbiome interactions that are gradually and slowly being characterized. An important force impacting host-drug-microbiome interactions is the selection force host-targeted drugs apply on the microbiome, which in turn can lead to impactful ecological and evolutionary adaptations in the microbiome itself. However, while the impact of many host-targeted drugs on the microbiome is widely appreciated, the bacterial targets of these drugs remain mostly unknown. In our study, we are screening large drug libraries to identify host-targeted drugs that inhibit bacterial growth and are aiming to identify the bacterial targets of these drugs. Such systematic understanding will reveal which host-targeted drugs resemble known categories of antibiotic drugs and if host-targeted drugs can point to new bacterial pathways that can be targeted by yet-to-be developed antibiotics.

Bacteria-host interactions

The human microbiome emerges as a major player in cancer biology. Groundbreaking studies in recent years uncovered clinically relevant associations between human microbiota and therapy success, and have identified mechanisms facilitating these interactions. Recent research of patient tumors revealed that many tumors harbor their own microbiome. These exciting findings lead to the appreciation that personalized cancer treatment should be tailored by the genetic makeup of both tumor and the microbiome. Our research of the tumor-microbiome is not anthropo-centric but microbial-centric, and aims to understand how do bacteria within tumors adapt to this unique microenvironment. We are investigating these evolutionary questions in diverse experimental systems and using both model bacterial lab species and clinical isolates cultured directly from tumors.

Updated information can be found at the Mitchell lab website

We are looking for rotation students to visit our lab and participate in one of our ongoing research projects. Different aspects of the projects require different toolsets ranging from experimental biology to quantitative biology and mathematical modeling. Rotation students will have a chance to acquire new skill-sets and develop expertise required for implementing a quantitative approach for understanding cell regulation, signaling and evolution. Interested students should email Amir directly and briefly describe their academic background, future plans and interest in the lab.

Current rotation projects:

• Investigating bacterial response to host-targeted drugs: As part of our research into the tumor-microbiome (tumor assosiated bacteria), we are testing how bacterial growth is inhibited by cytotoxic drugs that target cancer cells. Rotation students will run genetic screens in bacteria to identify bacterial toxicity and resistance mechanisms. In addition the students will test if bacteria can rapidly become drug resistance by evolutionary adaptation.
  
  
• Monitoring recovery dynamcis of melanoma cells in response to targeted therapy: The project involves examining and quantifying different aspects of cell behavior, population dynamics and adaptive resistance to targeted therapy. Rotation students will examine cellular behavior of established cell-lines and will clone and engineer new live-cell reporters for microscopy based assays.