Liedewij Laan Lab
The Laan lab is located in the Department of Bionanoscience, part of the Kavli Institute of Nanoscience at the Delft University of Technology. We are pioneering the emerging field of evolutionary cell biophysics.
Evolutionary Cell Biophysics
How is it possible that life is simultaneously highly robust on cell cycle timescales, yet also adaptable on evolutionary timescales? How do these properties emerge from the molecular building blocks of life? As pioneers of the emerging field of evolutionary cell biophysics, we are fascinated by how the physical and chemical properties of the building blocks, or components, of a cell (such as proteins, DNA, lipids etc. that need to obey physical and chemical laws) constrain and facilitate evolution of cellular functions. In this case a cellular function is the result of a complex, highly spatially and temporally regulated network, consisting of many different interacting components, “a biomolecular network”. The biomolecular network we focus on is symmetry breaking in budding yeast, which is the first step in polarity establishment and essential for proliferation. In budding yeast symmetry breaking is achieved by a biomolecular network of ~30 components which, through several regulatory feedback loops, form a localized protein pattern on the cell membrane. As a community we are starting to obtain a molecular understanding of how a living cell is organised by biomolecular networks on cell cycle timescales, however, how these networks reorganize over evolutionary timescales is still a major open question.
Why are these hard questions?
How biomolecular networks evolve is a complex problem for at least two reasons. First it is hard to know if a mutation in the network increases fitness and thus is adaptive, because this depends on the specific environment present when the mutation arose and we typically do not know the relevant environment for the evolutionary trajectory of existing species. Second, even if we know that a mutation is adaptive, it is hard to find out how adaptive mutations improve fitness, or even simply which biomolecular networks are affected for fitness increase, because in a living cell all biomolecular networks are connected.
Why do we care?
Foremost because these questions fascinate us. However we also hope that our fundamental findings help to (on the long run) better predict and control evolutionary processes, that have societal relevance, such as cancer progression or antibiotic resistance emergence, or the engineering of genetically stable drought resistant crobs.
We take a multidisciplinary approach. First we combine experimental evolution, quantitative cell biology and modelling in live cells to study how adaptive mutations increase the fitness of a biomolecular network. The strength of this approach is that we can directly test whether a mutation is adaptive. Nevertheless, in this system, it is still challenging to find out how adaptive mutations increase fitness at the molecular level due to the overwhelming complexity of a living cell. Therefore, we are also setting-up minimal in vitro systems. In these systems we know the complete network, so we can manipulate and control every component to determine its function for the network’s fitness and evolvability. Last but not least, we perform experimental evolution studies to test whether we how well we predict and steer evolution based on our acquired knowledge.
Christinne’s paper is submitted, good job Christine, curious, check it out on the Archiv.
Our Laan Lab SATAY pipeline is now openly available check it out here. Thanks very much to Wessel, Leila and Gregory. Gregory also leaves us for an exciting new job, we will miss you a lot and wish you lots of luck at the Erasmus MC.
March 17th and 18th
Enzo and Christine gave a talk at the APS.
Maaike successfully defended her Nanobiology BEP, congrats!
Floor (MEP) joins our lab, welcome!
We welcome our new labmember and mascot, Buddy, the LABrador!
The review paper about predicting evolution bottom-up illustrated in yeast cell polarity by Werner and Els is now published in Cells, well done!
Werner’s paper about predicting epistasis bottom-up through a coarse grained model of cell polarity is submitted!
We submitted Werner and Els’s invited review about how and when we understand cells well enough to predict evolution!
Our joined paper linking self-organization and evolvability with the Frey lab is on the BioRxiv now!
Laurie successfully defended her Applied Physics BEP, congrats!!
Thomas (MEP) and Maaike (BEP) join the lab, welcome!
With deep sadness we like to share that Mathia, after fighting cancer till the last day with optimism and joy, passed away. Thanks for the inspiration you were with your optimism, energy, kindness and passion, and how you embraced and enjoyed life!
Keije successfully defended his BEP.