Our Goals

We focus on the development of chemical tools to interrogate biological problems. For this, we are setting up a new chemistry lab within HWI. The close connection and proximity between the synthetic chemistry laboratory and the biochemical/structural biology facilities is absolutely vital to the synergistic nature inherent to chemical biology. Our main focus is the design and synthesis of photocaged ligands and substrates for time-resolved structural biology. These ligands can be released by exposure to short, bright pulses of light and initiate protein activity. The structure of the protein during its functional cycle, and hence their dynamics, can be observed in real time. Dynamics are a vital aspect of protein function, and misfunction, and are invaluable for the development of, for example, novel therapies or biocatalysts.

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Work Areas

Luciferases

At HWI, we are developing these photocaging methods for the time-resolved structural studies of Luciferases. These enzymes catalyze the oxidation of small molecules (luciferins) with molecular oxygen. As a side product of the oxidation, a photon of light is emitted. These proteins vary extensively in their structure and that of their substrates and are vital for many species. They are responsible for the blinking of fireflies, the warning signals of railroad worms and the glowing of sea pansies. The direct use of molecular oxygen for oxidation in biology is uncommon and we are interested to unravel the metastable intermediates associated with the high-energy states during this catalytic reaction.

Methods development

The collection of time-resolved X-ray diffraction and scattering is challenging and usually demands large quantities of sample due to the necessary constant sample replenishment. To support our experiments, we are developing novel sample delivery methods aimed at facilitating the experiments, making use of a variety of X-ray sources and reduce sample consumption.

Collaborative efforts

In close association with the BioXFEL team, we aim to provide the structural biology community with the tools necessary to design and successfully carry out time-resolved structural biology experiments. We can provide guidance on suitable photocaging approaches for each specific biological question as well as practical synthetic chemistry support in collaborative projects.

Biography

  • BSc&MChem in Medicinal Chemistry, University of Leeds (2011): industrial year at F. Hoffman-La Roche (Basel, Switzerland) and a Masters in organometallic chemistry (synthesis of cytotoxic NHC complexes).
  • PhD in Structural Molecular Biology, Astbury Centre, University of Leeds (2015): development of photocleavable compounds and the investigation of CoA regulation in enteric bacteria.
  • Postdoctoral Research Fellow at the Hamburg Centre for Ultrafast Imaging, Universität Hamburg, Germany (2019): development of microfluidic platforms for rapid mixing serial synchrotron diffraction data collection.

Education

  • BSc and MChem in Medicinal Chemistry (2011), University of Leeds UK. Industrial year at F. Hoffman-LaRoche (Basel, Switzerland) and MSc in Organometallic Chemistry
  • PhD in Structural Molecular Biology, University of Leeds (2015)
  • Postdoctoral Research Fellow at Hamburg Center for Ultrafast Imaging (Hamburg Germany).

Contact

Diana Monteiro
T: 716-898-8612
dmonteiro@hwi.buffalo.edu