Amyotrophic Lateral Sclerosis, Frontotemporal Dementia & Spinocerebellar Ataxia
With the aging of our populations, neurodegenerative diseases are increasing in their prevalence, posing an enormous societal burden. All of these disorders remain currently without a cure. My work focuses on understanding the molecular underpinnings of a group of closely-related diseases. In ALS, motor neurons in the motor cortex, brainstem, and spinal cord degenerate, resulting in rapidly progressive muscle weakness, paralysis, and death. While in FTD, degeneration affects frontal and temporal regions, resulting in most commonly behavioral changes and aphasia. SCA is characterized by problems with coordination, balance and speech, and stems from the demise of specific cerebellar neuron populations.
While these diseases may be sporadic in origin or caused by mutations in a heterogeneous set of genes, all cases present with pathological protein aggregates. We have focused on understanding the initial steps of this protein misbehavior in the hope to find novel therapeutic strategies to halt these devastating diseases in their early stages.
Decoding and engineering stress tolerance in plants and micro-organisms
Climate change is one of the most pressing problems of our time. As temperatures rise, the effects on agriculture will be immense: Water shortages, increase in droughts, salinification of soils due to poor irrigation practices, pests, etc. Most of our mainstay crops will not be able to withstand such stressful conditions. Fortunately, over the course of millions of years plants and microbes have evolved mechanisms to cope with such dire conditions (e.g., seed or spore dormancy, resurrection plants, thermophiles). On the other hand, a lot of tropical parasites are spreading exactly because of global warming. Numerous of these protists rely on their dormancy and stress tolerance for infection and propagation.
Therefore, we aim to better understand the molecular mechanism of dormancy and stress tolerance to come up with designer crops that will withstand the effects of climate change and novel strategies to combat emerging infectious diseases.
Designer membraneless organelles and novel bio-inspired nanomaterials
In our efforts to understand the rules governing membraneless organelle biogenesis and material properties in eukaryotes and prokaryotes, we have identified an underlying set of design principles. Based on these findings we have generated synthetic and tunable protein condensates, in vivo and in vitro. These condensates we are now engineering for novel protein-based regulatory circuits, catalytic nanoreactors encoding enzymatic reactions, and as designer nanomaterials.