Integrated Calendar

Antibodies
are produced to target any antigen using a finite set of gene fragments generating a huge diversity (>1010)
distinct structures. In contrast, we are unaware of a system that can produce analogous diversity in enzymes. Inspired by antibody repertoires,
I have developed the first strategy to design, synthesise, and experimentally
test repertoires comprising millions of enzymes. Using evolution-guided atomistic design
simulations, I designed thousands of protein fragments that exhibited
high structure and sequence diversity, including within the active-site pocket, which can be genetically assembled into full-length enzymes. I also developed an ML-based algorithm to select a subset of the designed fragments that would give rise to stable
and active proteins. Applied to a family of xylanases (sophisticated enzymes which are
critical in biomass degradation) I designed a repertoire comprising a million enzymes at a cost of 0.3¢
per enzyme. Screening with an activity-based probe revealed thousands of functional xylanases based on nearly 1,000 unique backbones. Advanced machine-learning methods uncovered important elements that discriminate active from inactive designs, enabling us
to design even more effective enzyme repertoires targeting, in principle, any desired substrate. Thus, enzyme repertoire design will enable a new generation of highly efficient and selective enzymes, while teaching us essential rules in biomolecular design.

The Messinian Salinity Crisis (MSC; 5.97-5.33 Ma) is considered an extreme environmental event driven by changes in climate and tectonics, which affected global ocean salinity and shaped the biogeochemical composition of the Mediterranean Sea. Yet, after more than 50 years of research, MSC chronology and events remains controversial. Recently drilled offshore wells in the Levant Basin retrieved for the first time a complete sedimentary record of the deep-basin Mediterranean MSC salt deposits and the underlying Pre-Evaporite unit. Analysis of this dataset changes the way these deposits have been perceived since the 1970’s, when they were first penetrated in their uppermost part during DSDP expeditions. Using sedimentology, chemistry, seismic interpretation, biostratigraphy, and astronomical tuning we show that Messinian salt deposition in the Eastern Mediterranean began during stage 1, and not stage 2 of the MSC. In contrast to the present paradigm, salt was deposited synchronously with gypsum deposition in the marginal and intermediate-depth basins. This occurred significantly earlier than the 50 kyr interval coined as the ‘MSC acme event’, ~300 kyr after the crisis began.
The one-kilometer-thick lower part of the evaporitic unit is composed of essentially pure halite, except for a thin transitional anhydrite layer at its base. The halite is undisturbed and homogeneous, lacking diverse features apparent in more proximal sections, indicating a deep-sea depositional environment. We find that distinct, meters-thick non-evaporitic intervals interbedded with the halite, previously thought to be clastic layers, are diatomites. While XRD analysis confirms an increase in clastic components in these sediments, they are composed primarily of well-preserved marine and freshwater planktonic diatoms. The occurrence of marine planktonic diatoms in these intervals indicates the input of Atlantic waters into the Mediterranean Basin during the deposition of the massive halite unit. In the second part of this talk I will couple lipid biomarker analysis with faunal and taxonomic evaluation of the diatom assemblages to try and answer the following question: why do we see this extreme abundance of diatoms, but a complete absence of calcareous-shelled forms of life within the MSC salt deposits?
This study demonstrates that brine formation, salt precipitation, and faunal extinction occurred at least in part in a deep, non-desiccated basin, with a restricted yet open Mediterranean-Atlantic connection that allowed inflow of oceanic water. A coeval onset of basinal halite and marginal gypsum precipitation calls for a revaluation of global-scale climatic and oceanographic models of the MSC, while substantially altering our understanding of the mechanisms governing the deposition of salt giants.