Complete List of Published Work in ORCID: https://orcid.org/0000-0002-3912-6095 , †Corresponding

A central dogma in cell migration is that chemotaxis (Brownian, osmotic) and durotaxis (material stiffness) are key extracellular drivers of cell migration. Cells live in an environment filled with viscous flowing fluid. We argue that extracellular fluid (ECF) properties not only control rate of diffusion, but shapes physical forces that a cell experiences. It is therefore plausible that fluid mechanical forces precede other taxis. To investigate ECF with single cell resolution from in vivo to in vitro, we develop and use a series of 4D optical and computational tools which we term as Spatial Adaptive Imaging (SAI) Platform.

Single Cell Fluidic Imaging We focus our effort in developing new technological advances in numerical modelling, devices, imaging technologies, and biomaterials to open new ways to understand the role of fluid pressure at all levels of a living biological system. Our goal is to develop new biological understanding of fluid-mediated mechanical forces (hydrostatic, hydrodynamic) and its prominence in promoting biological processes such as cell migration and aggregation, influencing gene expressions that reshape tissue and influence organ development, as well as informing disease progression in metastasis and thrombosis.

 PUBLICATIONS                                                                                                   

“Patterning Fluid Shear Stress Landscapes with Multiphoton Inner Laser Lithography (MILL) for Live Cell Adhesion and Translocation” Lim, Y.J., Xu, T., Zhang, J., Lin, H., , Li, Y., Zhang, Z., Hicks, S.M., Chudinov, I., Nechipurenko, D.Y., Gardiner, E.E., T Phan, W. M. Lee†  bioRxiv 2022.06.17.496569

 “Combined scattering, interferometry and fluorescence oblique illumination for live cell nanoscale imaging” Y Zheng*, Y J Lim*, H Lin, T Xu, C Longbottom , V Delghingaro-Augusto, Y L Thong, C Parish, E E Gardiner, W. M. Lee†  ACS Photonics  9, 12, 3876–3887 (2022)

 “Label-free multimodal quantitative imaging flow assay for intrathrombus formation in vitro.”  Y. Zheng, S. J. Montague, Y. J. Lim, T. Xu, T. Xu, E. E. Gardiner and W. M. Lee† (2021). Biophys J 120(5): 791-804.

 “Modified inverted selective plane illumination microscopy for sub-micrometer imaging resolution in polydimethylsiloxane soft lithography devices.” T. Xu, Y. J. Lim, Y. Zheng, M. Jung, K. Gaus, E. E. Gardiner and W. M. Lee† (2020)Lab Chip 20(21): 3960-3969.

 “Holo-UNet: hologram-to-hologram neural network restoration for high fidelity low light quantitative phase imaging of live cells.” Z. Zhang, Y. Zheng, T. Xu, A. Upadhya, Y. J. Lim, A. Mathews, L. Xie and W. M. Lee† (2020). Biomed Opt Express 11(10): 5478-5487.

“Quantifying Embolism: Label-Free Volumetric Mapping of Thrombus Structure and Kinesis in a Microfluidic System with Optical Holography.”X. F. He, S. J. Montague, X. Tao, E. E. Gardiner and W. M. Lee† (2018). " Advanced Biosystems 2(10).

Tissue-level Fluidic imaging   In vivo imaging studies of cell-fluids interactions are essential to test particular hypotheses and avoid the reductionist approach taken in in vitro systems. The next generation of deep tissue level fluid imaging need to provide sufficient visualisation for multiple cell population tracking under varying fluid stress. Within SAI platform, we have the next generation of deep tissue in vivo imaging tools which combines the latest in laser scanning methods, automation technologies, computer vision and machine learning techniques.

PUBLICATIONS                                                                                                          

"Computational single-objective scanning light sheet (cSOLS)", T  Xu, H Lin,Y J Lim, P R. Nicovich, K Gaus, and W.M.Lee†, APL Photonics 7, 081302 (2022)

"Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption."M. M. McDonald, W. H. Khoo, P. Y. Ng, … W. M. Lee, … P. I. Croucher and T. G. Phan. Cell 184(7): 1940 (2021)

“Raster Scanning Adaptive Optics for video rate correction and large field of view imaging” Y X Li, Y J Lim, Q K Xu, L Beattie, E E Gardiner, K Gaus, W Heath, W.M.Lee†, “” Biomedical Optics Express 2 1032 (2020)

“Flexible polygon-mirror based laser scanning microscope platform for multiphoton in-vivo imaging." Y. X. Li, V. Gautam, A. Brustle, I. A. Cockburn, V. R. Daria, C. Gillespie, K. Gaus, C. Alt and W. M. Lee† (2017). J Biophotonics 10(11): 1526-1537.

 “High   contrast   imaging   and   flexible   photomanipulation  for  quantitative in  vivo multiphoton imaging  with polygon  scanning microscope” Y X Li, S.J. Montague, A Brüstle, X.F. He, C. Gillespie, K Gaus, E.E. Gardiner, W.M.Lee† “ Journal of Biophotonics  11 (7), e201700341 (2018) 

 “In vivo cellular imaging of internal organs in small animals with GRIN fluorescence endomicroscopy: from fabrication to imaging”J K Kim*,   W.M Lee* et al, Nature Protocols  7 1456-1469(2012) 

Tools from the laboratory have been the subject of 4 international patents (WO2015113105A1, WO2017205892A1, WO2018045409A1, AUSIP-2019904929). Aside from that, our team regularly get invited to give oral presentations at over 22 international and national conferences (plenary, keynote, public lectures) organised by Google, ANSTO, Royal Society-NSW, TedXCanberra, National Optical Societies (OSA, EOS, AOS) and Fraunhofer institute and Czech Academy of Sciences. Our work received media coverage in TIME, ABC News, Sunrise (Ch7) ,SMH, The Australian, CBS News and Smithsonian.    

Open until filled

Seeing cells move under fluid pressure & Beating the limits of Phototoxicity

Our mission is to develop adaptive, low phototoxicity imaging tools that can map out long range directed cell migration under fluid pressure (static and dynamic) that occurs during organ development, injury and infection.Fluid-mediated mechanical forces (hydrostatic, hydrodynamic) have emerged as a prominent player in promoting biological processes such as cell migration and aggregation, influencing gene expressions that reshape tissue and influence organ development, as well as informing disease progression in metastasis and thrombosis.

To fulfil our mission, we shall be recruiting three PhD candidates join a small and highly dynamic team of researchers (biophysicists, biochemists, computational biologists) to work on the following projects

1. Single Cell-level Fluidics Imaging

     Stromal cell aggregating and migrating under changing extracellular fluid pressure (ECF)

This PhD will work in an international group of biophysicists, and lead in the application of bespoken quantitative bioimaging technologies to study how hydrostatic and hydrodynamic fluid forces influence long range migratory pattern of mammalian cells. The student will study how individual and groups of stromal cells modify their cytoskeleton (through transmembrane proteins) to move into a 3D ECF rich environment. Novel 4D computational single cell approaches will be explored.

2. Tissue-level Fluidics Imaging

    Tracking and study cell migrate in ECF rich microenvironment. 

Cells migrating in microenvironment encounters soft fibrils matrix and changing fluid pressure under active flow and varying viscosity. This PhD will work with group of biophysicists, cancer biologists, immunologists, to develop study how blood cells, immune cells and cancer migrating within living organs (lymph node, blood vessels and tumour) using actomyosin machinery that alters local micronenvironment. Novel adaptive imaging solutions using cutting edge multiphoton tools and new computational imaging packages will be used to study these processes.

3. Engineering ECF for 3D self assembly of spheroid and organoid.

     Disease Avatars in a bubble

Through our understanding of cell movement, aggregating in both in vitro and in vivo settings, alongside with our Spatial Adaptive Imaging and lithography (SAIL) tools, we will design to create new cell-based assays that can accelerate, we set out to create micro-Avatars (organiod, spheriods) to be used for human disease diagnosis and therapy.  This PhD will be focus on using active flow with engineered synthetic fluids to developed template-free 3D spheroid and organoid. 

Unlimited access to cutting edge biophysical tools: Both candidates will have unlimited access to a host of industry-grade 4D optical imaging and computational platforms developed and designed by the Biofluidic Group (OBIG) that are located at John Curtin School of Medical Research (JCSMR) at the Australian National University – Canberra, ACRF INCITE Centre at Garvan Institute of Medical Research – Sydney, Doherty Institute at Melbourne – ARC LIEF.  Projects will be embedded in JCSMR, Garvan and Doherty graduate programs with excellent supervision and a dynamic and international community of international PhD students.

Our expectations: Applicants are required to hold a 1st Class Honours or Master’s degree in the biophysics and/or biological sciences or other basic science disciplines in physics, chemistry and biology. A good command of the English language is necessary.  We also welcome cell biologists with previous experience in advanced fluorescence microscopy as well as computational biologists with experience advanced image data analysis. At the ANU, we strongly support equal opportunity and diversity. We welcome all applicants regardless of sex, nationality, ethnic or social background, religion or worldview, disability, age, sexual orientation or gender identity. We are committed to creating family-friendly working conditions. We actively encourage applications by women.

Please send an electronic application including your CV, a short motivation letter and two references to Dr W M Steve Lee

Through the comprehensive research and teaching program in Optical Biofluidics Imaging Group at ANU, we have trained and graduated over 41 researchers (postdoctoral, PhDs, Masters, Honors Project, summer scholars) that has taken up senior research or industry positions - tenure track position at Beijing University of Posts and Telecommunications, postdoctoral position at Rockefeller University, University of Adelaide, University research fellowship (Birmingham) and EMBO fellowship. Positions in established biomedical industry including Therapeutic Goods Administration (TGA), Cochlear Australia , ResMed (Sydney), Beijing Genomics Institute. Research undergraduates from the laboratory have obtained highest distinction from Australian National University, Institution of Engineering and Technology and Harvard-MIT Program in Health Sciences and Technology.

Junior Research Staff (Primary Supervisor)

2020- 2023 :     Mr Zhiduo Zhang                  ,Snr CVR, Droneshield   

2022 - 2023:      Mr Andrew Waddell,              Royal Australian Navy

2021 - 2022:      Mr Hanqi Lin ,                       UC Santa Cruz (MSc)        

2021 - 2022:      Mr Kwun Ting (Jasper) Li ,     ANU Academic Tutor        

2020 - 2022:      Mr Junxiang Zhang ,             ANU Academic Tutor 

2017 - 2020:      Mr Tao Xu ,                          Toyota Graduate Training Program    

2018 - 2019:     *Dr Yuanqing (Alex) Ma ,        EMBO Fellow, Marseille France    

2017 - 2018:      Dr Samantha Montague,        Research Fellow,             

2016 - 2017:      Dr Roland Fleddermann,         Research Fellow,                          

2014 - 2015:      Mr Zijian Cen,                        Senior Product Analytics                              

Graduate students (Primary supervisor)

2020- 2023 :     Mr Zhiduo Zhang MPhil Candidate , Snr CVR, Droneshield 

2017 - 2022:     Mr Avinash Upadhya- PhD Candidate, Postdoctoral fellow, Uni of Adelaide

2017 - 2021:     Ms Yujie Zheng, PhD Candidate, Optical Engineer, BGI/MGI

2015 -  2019:    Mr Yongxiao Li, PhD Candidate, Associate Professor(Research)

2014 -  2018:     Miss Xuefei (Sherry) He, PhD Candidate  Imaging Engineer, HiSilicon

2014 -  2018:     Miss Tahseen Kamal, PhD Candidate Research Associate UNSW

2016 -  2017:    *Miss Wei Zhong, Master Student (Uni Twente, Netherlands)  Research Scientist, Science Sport

2013 -  2016:     Mr Niko Eckerskorn, PhD Candidate (Australian National University)  Analytics Engineer - CoreLogic RP Data

2015 -  2016:    *Mr Wengou Zhu, Visiting PhD candidate(Sun Yat University, China)        Lecturer

2014 – 2015:    *Mr Redmar Vileg, Visiting Master Student (Uni Twente, Netherlands) PhD student, Leiden Uni 

2013 – 2014:     Mr Huang Longyao, Master by Research  (Australian National University)

2013 – 2014:    *Miss Sjoukje Schoustra, Visiting Master Student (Uni Twente, Netherlands)   PhD student, Twente Uni

2013 – 2014 :   *Miss Li Li,Visiting PhD candidate(Sun Yat University, China) Research Engineering Huawei

Undergraduate

2020 - 2021:     Mr Hanqi Lin                          Imaging Technician, ANU  

2019 - 2020:     Mr Junxiang Zhang                 Imaging Technician, ANU

2019 - 2020:     Mr Sanjeev Parbaharan

2018           :    *Ms Hui Wang Undergraduate, Tsinghua University

2017-  2018:     Mr Yonglin Ren

2017-  2017:     Mr Oliver Johnson, University Medal  | ANU-HST-MIT summer scholar

2016 - 2016 :    Ms Emily Campbell  Tillyard prize recipient | ANU-HST-MIT Summer scholar

2016-  2017:     Mr Tienan Xu  ANU-PhD student

2015 - 2016:     Mr Thomas McMenamin  Bioscout-Head R&D

2015 - 2016:     Mr Avinash Upadhya, University Medal  | ANU-HST-MIT summer scholar ANU-PhD student

2015 - 2016:     Mr Yang Lu  CSIRO-PhD student 

2015 - 2016:     Mr Tao Xu    ANU-MSc student

2014 - 2015:     Mr Misha Petkovic System Engineer, Seeing Machine

2015 - 2016      Miss Yi Du

2015 - 2016      Miss Yujie Zheng   ANU-PhD student

2015 - 2016      Mr Lyle Halliday,  University Medal, IET Medal  System Engineer, S Medical

2014 - 2015      Mr Zachary Shafron,  Honorable mention(undergraduate project) System Engineer, Thales

2013 –2015      Mr Avinash Upadhya, Yao Su Student Research Award ANU-PhD student

2014 –2015      Ms Rachel Watkins,YouFab Global Creative Awards, Finalist Teacher (STEM)

2014 –2015      Mr David Wright

2014 –2015      Mr Jaden Rubstein

2014 –2015      Mr Zi Cen (Kenny) Senior Product Analytics Engineer ResMed

2014 –2015      Mr Alan Harrison 

2013 –2014      Miss Siti Mohd Shariaf   

* visiting