Paulsson Lab Homepage

Department of Systems Biology
Harvard Medical School

Many genes, RNAs and proteins are present in such low numbers that fluctuations in abundances between otherwise identical cells are inevitable. Such ‘noise’ has now been implicated in a wide range of processes in a variety of organisms. Numerous studies have shown how noise generates phenotypic heterogeneity in cell behavior, how cells can suppress deviations when fluctuations are selected against, and how they can functionally exploit variability for increased fitness. The sources and dynamics of the fluctuations have also been analyzed in great detail, for example focusing on intrinsic versus extrinsic contributions, ‘bursty’ transcription and translation, or the transmission of noise in cascades. The recent explosion of fluctuation studies may be the mere beginning of a sea change in experimental cell biology, as fluorescent reporters are making quantitative single cell experiments routine.

Many insights have been gained from these studies, but as we and others have repeatedly shown, the conventional approaches can also be very misleading. The lack of organizing physical laws combined with low-resolution data and model plasticity make retrodiction and story-telling too easy, while most ‘predictions’ simply interpolate known principles. In some ways the situation is not unlike that of early astronomy: even without any coherent theory, the Babylonian Astronomical Diaries predicted certain celestial events with higher accuracy than the first applications of Newton’s laws, by simply mimicking observed patterns.

Our lab is committed to addressing this problem through a combination of approaches. We study several specific mechanisms in detail, but also place a great emphasis on broad theorems and mathematical methods, and on new libraries and novel experimental counting assays.