Forcing cells to change lineages

Thomas Graf, Tariq Enver

Abstract | The ability to produce stem cells by induced pluripotency (iPS reprogramming) has rekindled an interest in earlier studies showing that transcription factors can directly convert specialized cells from one lineage to another. Lineage reprogramming has become a powerful tool to study cell fate choice during differentiation, akin to inducing mutations for the discovery of gene functions. The lessons learnt provide a rubric for how cells may be manipulated for therapeutic purposes.

http://www.nature.com/nature/journal/v462/n7273/pdf/nature08533.pdf

Synthetic biology: understanding biological design from synthetic circuits

Shankar Mukherji and Alexander van Oudenaarden

Abstract | An important aim of synthetic biology is to uncover the design principles of natural biological systems through the rational design of gene and protein circuits. Here, we highlight how the process of engineering biological systems — from synthetic promoters to the control of cell–cell interactions — has contributed to our understanding of how endogenous systems are put together and function. Synthetic biological devices allow us to grasp intuitively the ranges of behaviour generated by simple biological circuits, such as linear cascades and interlocking feedback loops, as well as to exert control over natural processes, such as gene expression and population dynamics.

http://www.nature.com/nrg/journal/v10/n12/pdf/nrg2697.pdf

Bacterial responses to photo-oxidative stress

Eva C. Ziegelhoffer and Timothy J. Donohue

Abstract | Singlet oxygen is one of several reactive oxygen species that can destroy biomolecules, microorganisms and other cells. Traditionally, the response to singlet oxygen has been termed photo-oxidative stress, as light-dependent processes in photosynthetic cells are major biological sources of singlet oxygen. Recent work identifying a core set of singlet oxygen stress response genes across various bacterial species highlights the importance of this response for survival by both photosynthetic and non-photosynthetic cells. Here, we review how bacterial cells mount a transcriptional response to photo-oxidative stress in the context of what is known about bacterial stress responses to other reactive oxygen species.

http://www.nature.com/nrmicro/journal/v7/n12/pdf/nrmicro2237.pdf

The spectrum of latent tuberculosis: rethinking the biology and intervention strategies

Clifton E. Barry 3rd, Helena I. Boshoff, Véronique Dartois, Thomas Dick, Sabine Ehrt, JoAnne Flynn, Dirk Schnappinger, Robert J. Wilkinson and Douglas Young

Abstract | Immunological tests provide evidence of latent tuberculosis in one third of the global population, which corresponds to more than two billion individuals. Latent tuberculosis is defined by the absence of clinical symptoms but carries a risk of subsequent progression to clinical disease, particularly in the context of co-infection with HIV. In this Review we discuss the biology of latent tuberculosis as part of a broad range of responses that occur following infection with Mycobacterium tuberculosis, which result in the formation of physiologically distinct granulomatous lesions that provide microenvironments with differential ability to support or suppress the persistence of viable bacteria. We then show how this model can be used to develop a rational programme to discover effective drugs for the eradication of M. tuberculosis infection.

http://www.nature.com/nrmicro/journal/v7/n12/pdf/nrmicro2236.pdf