The coordinated transport of proteins and nucleic acids between the nucleus and the cytosol is vital for proper gene expression and cell function, and hijacked by viruses to propagate. In this PhD project, you will devise new methods to study the physical and molecular mechanisms that make transport selective. This is a formidable challenge that requires multiple disciplines, physics, biology and chemistry, to work hand in hand.
The hallmark of eukaryotic cells is the their compartmentalisation into the nucleus, which harbours our genes, and the cytosol in which the genetic code is translated into functional proteins. This spatial separation enables sophisticated regulation, but also poses a tremendous logistical challenge to the cell as nucleic acids and proteins have to be shuttled across the nuclear envelope. Macromolecular transport occurs through 40 nm wide channels in nuclear pore complexes that perforate the nuclear envelope. Transport is gated by the nuclear pore permselectivity barrier, a meshwork of intrinsically disordered proteins and transport receptors that fills the channels; yet, how this meshwork enables rapid yet highly selective transport is not well understood.
In a multidisciplinary environment, you will learn to create bottom up biosynthetic models of the permselectivity barrier and develop advanced optical microscopy techniques to track molecular transport within these nanoscale barriers. The experimental work will be accompanied by theoretical work to aid the analysis of the experimental data and develop an understanding of the molecular and soft matter physics underpinning selective nucleo-cytoplasmic transport.
In this project, you will put physics and chemistry tools to the benefit of understanding biology. This will provide new insight into how nucleo-cytoplasmic transport is regulated, and ultimately help to devise new strategies to interfere with diseases, such as viral infection, and to design advanced biomaterials (e.g. for biosensors).
Suitable CANDIDATES would have a background in biophysics, soft matter physics, physical chemistry, biomedical engineering or a closely related field, and keen interest in multidisciplinary work. Experience in advanced optical microscopy and/or in scientific programming are an advantage.
Further information about this project and how to apply can be found on our website.