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.
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.
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.
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.
- X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease. Science. 2021 May 7;372(6542):642-646. doi: 10.1126/science.abf7945. Epub 2021 Apr 2.
- Homogeneous batch micro-crystallization of proteins from ammonium sulfate. Acta Crystallogr D Struct Biol. 2021 Feb 1;77(Pt 2):194-204. doi: 10.1107/S2059798320015454. Epub 2021 Jan 26.
- Microfluidic polyimide gas dynamic virtual nozzles for serial crystallography. Rev Sci Instrum. 2020 Aug 1;91(8):085108. doi: 10.1063/5.0012806.
- Need for Speed: Examining Protein Behavior during CryoEM Grid Preparation at Different Timescales. Klebl DP, Gravett MSC, Kontziampasis D, Wright DJ, Bon RS, Monteiro DCF, Trebbin M, Sobott F, White HD, Darrow MC, Thompson RF, Muench SP.Structure. 2020 Nov 3;28(11):1238-1248.e4. doi: 10.1016/j.str.2020.07.018. Epub 2020 Aug 18.
- Sample deposition onto cryo-EM grids: from sprays to jets and back. Klebl DP, Monteiro DCF, Kontziampasis D, Kopf F, Sobott F, White HD, Trebbin M, Muench SP.Acta Crystallogr D Struct Biol. 2020 Apr 1;76(Pt 4):340-349. doi: 10.1107/S2059798320002958. Epub 2020 Mar 25.
- 3D-MiXD: 3D-printed X-ray-compatible microfluidic devices for rapid, low-consumption serial synchrotron crystallography data collection in flow. Monteiro DCF, von Stetten D, Stohrer C, Sans M, Pearson AR, Santoni G, van der Linden P, Trebbin M.IUCrJ. 2020 Jan 16;7(Pt 2):207-219. doi: 10.1107/S2052252519016865. eCollection 2020 Mar 1.
- Structural Kinetics of MsbA Investigated by Stopped-Flow Time-Resolved Small-Angle X-Ray Scattering. Josts I, Gao Y, Monteiro DCF, Niebling S, Nitsche J, Veith K, Gräwert TW, Blanchet CE, Schroer MA, Huse N, Pearson AR, Svergun DI, Tidow H.
- Evaluation of serial crystallographic structure determination within megahertz pulse trains. Yefanov O, Oberthür D, Bean R, Wiedorn MO, Knoska J, Pena G, Awel S, Gumprecht L, Domaracky M, Sarrou I, Lourdu Xavier P, Metz M, Bajt S, Mariani V, Gevorkov Y, White TA, Tolstikova A, Villanueva-Perez P, Seuring C, Aplin S, Estillore AD, Küpper J, Klyuev A, Kuhn M, Laurus T, Graafsma H, Monteiro DCF, Trebbin M, Maia FRNC, Cruz-Mazo F, Gañán-Calvo AM, Heymann M, Darmanin C, Abbey B, Schmidt M, Fromme P, Giewekemeyer K, Sikorski M, Graceffa R, Vagovic P, Kluyver T, Bergemann M, Fangohr H, Sztuk-Dambietz J, Hauf S, Raab N, Bondar V, Mancuso AP, Chapman H, Barty A.Struct Dyn. 2019 Dec 4;6(6):064702. doi: 10.1063/1.5124387. eCollection 2019 Nov.
- A cryo-EM grid preparation device for time-resolved structural studies. Kontziampasis D, Klebl DP, Iadanza MG, Scarff CA, Kopf F, Sobott F, Monteiro DCF, Trebbin M, Muench SP, White HD.IUCrJ. 2019 Sep 5;6(Pt 6):1024-1031. doi: 10.1107/S2052252519011345. eCollection 2019 Nov 1.
- Solution blow spinning of polymer/nanocomposite micro-/nanofibers with tunable diameters and morphologies using a gas dynamic virtual nozzle. Vasireddi R, Kruse J, Vakili M, Kulkarni S, Keller TF, Monteiro DCF, Trebbin M.Sci Rep. 2019 Oct 4;9(1):14297. doi: 10.1038/s41598-019-50477-6.
- A microfluidic flow-focusing device for low sample consumption serial synchrotron crystallography experiments in liquid flow. Monteiro DCF, Vakili M, Harich J, Sztucki M, Meier SM, Horrell S, Josts I, Trebbin M.J Synchrotron Radiat. 2019 Mar 1;26(Pt 2):406-412. doi: 10.1107/S1600577519000304. Epub 2019 Feb 13.
- Megahertz serial crystallography. Wiedorn MO, Oberthür D, Bean R, Schubert R, Werner N, Abbey B, Aepfelbacher M, Adriano L, Allahgholi A, Al-Qudami N, Andreasson J, Aplin S, Awel S, Ayyer K, Bajt S, Barák I, Bari S, Bielecki J, Botha S, Boukhelef D, Brehm W, Brockhauser S, Cheviakov I, Coleman MA, Cruz-Mazo F, Danilevski C, Darmanin C, Doak RB, Domaracky M, Dörner K, Du Y, Fangohr H, Fleckenstein H, Frank M, Fromme P, Gañán-Calvo AM, Gevorkov Y, Giewekemeyer K, Ginn HM, Graafsma H, Graceffa R, Greiffenberg D, Gumprecht L, Göttlicher P, Hajdu J, Hauf S, Heymann M, Holmes S, Horke DA, Hunter MS, Imlau S, Kaukher A, Kim Y, Klyuev A, Knoška J, Kobe B, Kuhn M, Kupitz C, Küpper J, Lahey-Rudolph JM, Laurus T, Le Cong K, Letrun R, Xavier PL, Maia L, Maia FRNC, Mariani V, Messerschmidt M, Metz M, Mezza D, Michelat T, Mills G, Monteiro DCF, Morgan A, Mühlig K, Munke A, Münnich A, Nette J, Nugent KA, Nuguid T, Orville AM, Pandey S, Pena G, Villanueva-Perez P, Poehlsen J, Previtali G, Redecke L, Riekehr WM, Rohde H, Round A, Safenreiter T, Sarrou I, Sato T, Schmidt M, Schmitt B, Schönherr R, Schulz J, Sellberg JA, Seibert MM, Seuring C, Shelby ML, Shoeman RL, Sikorski M, Silenzi A, Stan CA, Shi X, Stern S, Sztuk-Dambietz J, Szuba J, Tolstikova A, Trebbin M, Trunk U, Vagovic P, Ve T, Weinhausen B, White TA, Wrona K, Xu C, Yefanov O, Zatsepin N, Zhang J, Perbandt M, Mancuso AP, Betzel C, Chapman H, Barty A.Nat Commun. 2018 Oct 2;9(1):4025. doi: 10.1038/s41467-018-06156-7.
- The Mechanism of Regulation of Pantothenate Biosynthesis by the PanD-PanZ·AcCoA Complex Reveals an Additional Mode of Action for the Antimetabolite N-Pentyl Pantothenamide (N5-Pan). Arnott ZLP, Nozaki S, Monteiro DCF, Morgan HE, Pearson AR, Niki H, Webb ME.Biochemistry. 2017 Sep 19;56(37):4931-4939. doi: 10.1021/acs.biochem.7b00509. Epub 2017 Sep 7.
- The structure of the PanD/PanZ protein complex reveals negative feedback regulation of pantothenate biosynthesis by coenzyme A. Monteiro DCF, Patel V, Bartlett CP, Nozaki S, Grant TD, Gowdy JA, Thompson GS, Kalverda AP, Snell EH, Niki H, Pearson AR, Webb ME.
- Growth kinetics of bacterial pili from pairwise pilin association rates. Monteiro DC, Kamdoum WV, Paci E.PLoS One. 2013 May 7;8(5):e63065. doi: 10.1371/journal.pone.0063065. Print 2013.
- Formation of a heterooctameric complex between aspartate α-decarboxylase and its cognate activating factor, PanZ, is CoA-dependent. Monteiro DC, Rugen MD, Shepherd D, Nozaki S, Niki H, Webb ME.Biochem Biophys Res Commun. 2012 Sep 28;426(3):350-5. doi: 10.1016/j.bbrc.2012.08.084. Epub 2012 Aug 24.
- Enhanced cytotoxicity of silver complexes bearing bidentate N-heterocyclic carbene ligands. Monteiro DC, Phillips RM, Crossley BD, Fielden J, Willans CE.Dalton Trans. 2012 Apr 7;41(13):3720-5. doi: 10.1039/c2dt12399a. Epub 2012 Feb 13.
- PhD in Structural Molecular Biology, Astbury Centre, University of Leeds (2015): Thesis title: Development of photocleavable compounds and the investigation of CoA regulation in enteric bacteria.
- 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).