Entry Date:
October 22, 2008

Love Lab

Principal Investigator J Love

Project Website http://web.mit.edu/lovelab/

The Love Lab is exploring the heterogeneity present in populations of cells and characterizing the dynamic biological responses of individual cells subjected to defined perturbations. We develop new processes for analyzing large numbers of individual living cells quantitatively and dynamically. The primary approach uses simple technologies, based on soft lithography or unconventional nanofabrication, to measure multiple characteristics of single cells, and from those data, we aim to construct detailed profiles that describe the state and evolution of the cell itself or the multicellular population of which it is a member. The applications for these technologies that we are pursuing include clonal selection for bioprocess manufacturing, discovery of new immunotherapies, and immunological monitoring for diagnosis and biomedical research in clinical immunology.

The lab itself is an interdisciplinary and team-oriented environment. We apply concepts and techniques from surface chemistry, materials science, physics, and chemical engineering to address biological questions in immunology, microbiology, systems biology, and bioprocess engineering. Particular areas of emphasis in clinical immunology presently are infectious diseases and autoimmune disorders. We value expertise from a range of backgrounds relevant to these areas of research.

The long-term objectives of our work are to understand how heterogeneity in populations of cells affects their collective behaviors as a system, and to gain insights into the biological variations present in unique and rare cells from those populations. We also aim to facilitate the transfer of these technologies into clinical laboratories for extended use in biomedical research.

Individual, living cells are complex, analog signal processors. That is, they use biochemical processes to transform some number of inputs, such as ligands for receptors, to produce some output (move, regulate certain genes, activate pathways for extracellular secretions). Both the unique, accumulated history of stimuli experienced by the cell and stochastic molecular events strongly influence these outcomes. Each cell is, therefore, distinct, and collections of cells are not uniform populations, but rather complex ensembles comprising many individuals. Modern biology has made remarkable progress in understanding the mechanisms by which cells operate (and cooperate in multicellular organisms), but many of these insights result from studying the average states and functions of cells. There is an increasing realization, however, that characterizing the heterogeneities of cells is important for describing the time-dependent responses of complete biological systems—for example, the coordinated cellular immune responses to infectious agents.

New technologies capable of measuring multiple characteristics of single cells in a quantitative manner over time, and in large numbers (10,000 to 1,000,000), would accelerate the understanding of the macroscopic responses of multicellular biological systems as well as the collective properties of clonal populations (bacterial colonies, mammalian cell lines). Broadly, our research combines ideas from materials science and interfacial chemistry to enable new micro- and nanotechnologies for studying the biology of complex collections of cells in a quantitative manner. We focus on developing methods to determine multiple qualities that define the identity, function, and genetic content of individual cells. Using these tools, we aim to construct detailed profiles that describe the state and evolution of a multicellular population. Such profiles will make it possible (1) to understand the precise cellular signatures that characterize an immune response to one disease state or another, (2) to examine the biological variations that can arise in clonal populations of cells used for bioprocess manufacturing, and (3) to identify extremely rare cells within large libraries of variants (e.g, ones producing unique engineered enzymes or antibodies).