"The recent years have witnessed an explosive growth in the numbers of new materials with fascinating properties and high application potential. Two-dimensional materials are at the focus of interest, in particular graphene but also two-dimensional niobium diselenide, molybdenum disulfide, hexagonal boron nitride, mono-layer bismuth strontium calcium copper oxide, and a variety of other layered materials. This proposal builds on my recognized expertise and experience in the areas of atomically resolved studies and atomic level manipulation of new materials using electron beams in a transmission electron microscope. Instead of observing random, beam-driven or contamination-induced variations in image sequences, I plan to carry out targeted, controlled experiments to study atomic scale modifications in real time. I will establish new experimental approaches to study the properties of low-dimensional systems, light-element- and radiation-sensitive samples. The first key objective is controlled in-situ manipulation, via imposing chemical modifications that are locally activated by the electron beam and directly followed in real time. The second and strongly interlinked objective is to alleviate the effects of radiation damage by different new approaches (beyond low-voltage imaging), by making use of new statistical methods that exploit the multiplicity of identical configurations. I aim to transfer very recent developments for low-dose imaging from structural biology to the case of point defect configurations in a crystalline material, to allow the identification of atomic configurations that are currently not accessible as they do not withstand the electron dose that would be needed for their identification. Overall, this project will provide fundamental new insights to the science and applications of some of today's most promising new materials, new routes to tailor their properties, and methodological advances that will reach well beyond our target materials."