About me
I am a biophysicist with background in signal processing and telecommunications. I completed my doctoral study in Tampere University of Technology in January 2016 with prof. Andre Ribeiro. Later, I worked as a postdoc with prof. Aleksandra Walczak (École Normale Supérieure) and prof. Nathalie Dostatni (Institut Curie) in Paris, France. In 2021, I returned to Finland to work in MET faculty as a postdoc researcher and from 2023 as the Research Council of Finland’s Research fellow.
I have always been fascinated by living organisms as dynamic systems, in which individual cells’ nonlinear convoluting behaviors are hidden in the population and steady-state statistics. Many behaviors, tailored over billions of years of evolution to ensure the organisms’ survival, operate either in equilibrium with their environments or at the physical limit. My research goal is to uncover these design principles in different organisms and cell types through the use of modeling and quantitative in vitro experiments. These principles can help redefine what “healthy” should be rather than metric means.
Research topics
My research has always been at the interface between theoreticians (myself included) and experimentalists, where we combine state-of-the-art tools of genetics, imaging, machine learning and computational modeling to achieve mechanistic understandings of biological phenomena. The central theme of my study is the balance between speed, accuracy and energy consumption in biological phenomena and how different cell types navigate within this balance to perform their respective functions.
Cell-to-cell communication via Calcium signaling cascades.
with Teemu Ihalainen, Soile Nymark, Arri Priimägi and Jari Hyttinen
Tightly connected epithelial tissues achieve complex behaviors largely by coordinating electrophysiological activities across individual cells through ion channels. These electrophysiological activities, with the most well-known being calcium signaling, determine cells’ immediate response to external stimuli by triggering transduction signaling pathways. Electrophysiological signals, despite the short time scale (from milliseconds to tens of minutes), are rarely static. Transduction signaling molecules such as calcium can also introduce latent but much longer-term changes in cells by affecting the Gene Regulatory Network (GRN), which operates at a much slower time scale (in hours or days). This can alter drastically, sometimes irreversibly, subsequent cellular behaviors by modulating protein subunits involved in the electrophysiological responses.
In this multidisciplinary spearhead, we aim to study the linkage between these two very different yet intertwining components and their roles in tissue behaviors. We will employ state-of-the-art measurement techniques, particularly in live imaging, to simultaneously apply stimulations to the tissues and capture the triggered calcium dynamics. The captured calcium responses to stimuli of different scales are then combined by integrating the principles of statistical biophysics and machine learning to characterize the trajectory of tissue behaviors over time. We first focus on epithelial cells, in particular Madin-Darby Canine Kidney and Retina Pigment Epithelium, as model tissues.
Gene expression in development
Postdoc project, with Aleksandra Walczak and Nathalie Dostatni
During my post-doctoral training, I studied the formation of gap genes’ expression patterns and its robustness in Drosophila melanogaster earlier embryogenesis. This concerns how cell identity, usually determined by the expression of specific genes, is established at the correct time and correct location in space to ensure the reproducibility of developmental patterns and the emergence of properly proportioned individuals despite their varying size and growth rate. The work is at the very interface between biology and physics, with the aim to explain quantitatively the mechanisms responsible for the pattern formation via means of modelling and explore/validate them via MS2-MCP RNA-tagging approach for live monitoring of transcription.
Dynamics of genetic circuits
Doctoral thesis with Andre Ribeiro
In genetic circuits, the constituent genes do not interact only between themselves but also with regulatory molecules of the host cells that support the circuits’ operation and by the environmental conditions. These factors, along with the intrinsic noise in gene expression, govern the functioning of the circuits. As such, to understand the structure of natural circuits and to engineer functional synthetic circuits, one needs to characterize thoroughly how external factors and perturbations from the environment may affect their behavior. In my doctoral studies, I focused on two major topics: (1) the dynamics of genetic circuits in specific contextual settings and (2) regulatory mechanisms of transcription in bacterium Escherichia coli.
Selected publications
*Equal contribution
1. HM Peussa, C Fedele, H Tran, M Marttinen, J Fadjukov, E Mäntylä, A Priimägi, S Nymärk, TO Ihalainen, Light-induced nanoscale deformation in azobenzene thin film triggers rapid intracellular Ca2+ increase via mechanosensitive cation channels, Advanced Science, 10 (15), 2206190, 2023.
2. G Fernandes*, H Tran*, M Andrieu, Y Diaw, C Perez-Romero, C Fradin, M Coppey, A Walczak, N Dostatni, Synthetic reconstruction of the hunchback promoter specifies the role of Bicoid, Zelda and Hunchback in the dynamics of its transcription, eLife, 11, e74509, 2022.
3. H Tran, A Walczak, N Dostatni, Constraints and limitations on the transcriptional response downstream of the Bicoid morphogen gradient, Current Topic in Developmental Biology: Gradients and Tissue Patterning, 2020.
4. H Tran, CA Perez-Romero, T Ferraro, C Fradin, N Dostatni, M Coppey and AM Walczak, LiveFly - a toolbox for the analysis of transcription dynamics in live Drosophila embryos. Morphogen Gradients, protocol series Methods in Molecular Biology, Springer, pp 193-195, 2018.
5. CA Perez-Romero, H Tran, M Coppey, AM Walczak, C Fradin, N Dostatni, Live imaging of mRNA transcription in Drosophila embryos. Morphogen Gradients, protocol series Methods in Molecular Biology, Springer, pp 165-182, 2018.
6. H Tran, J Desponds, CPA Romero, M Coppey, C Fradin, Dostatni N, AM Walczak, Precision in a rush: trade-offs between positioning and steepness of the hunchback expression pattern, PLOS Computational Biology, e1006513, 2018.
7. T Lucas*, H Tran*, CPA Romero, A Guillou, C Fradin, M Coppey, AM Walczak, N Dostatni, 3 minutes to precisely measure morphogen concentration, PLOS Genetics, e1007676, 2018.
8. J Desponds, H Tran, T Ferraro, T Lucas, CP Romero, A Guillou, C Fradin, M Coppey, N Dostatni, AM Walczak, Precision of readout at the hunchback gene, PLOS Computational Biology, 12 (12), e1005256, 2016.
9. SMD Oliveira*, Antti Häkkinen*, J Lloyd-Price, H Tran, V Kandavalli, AS Ribeiro, Temperature-dependent model of multi-step transcription initiation in Escherichia coli based on live single-cell measurements, PLOS Computational Biology, 12 (10), e1005174, 2016.
10. VK Kandavalli*, H Tran*, JG Chandraseelan, AS Ribeiro, Effects of σ factor competition on the in vivo kinetics of transcription initiation in Escherichia coli, BBA Gene Regulatory Mechanisms, 1859, 2016.
11. SMD Oliveira*, R Neeli-Venkata*, NM Goncalves, JA Santinha, L Martins, H Tran, J Mäkelä, A Gupta, M Barandas, A Häkkinen, J Lloyd-Price, JM Fonseca, and AS Ribeiro, Increased cytoplasm viscosity hampers aggregate polar segregation in Escherichia coli, Molecular Microbiology 99(4), 2016.
12. H Tran, SMD Oliveira, NM Goncalves, AS Ribeiro, Kinetics of the cellular intake of a gene expression inducer at high concentrations, Molecular BioSystems 11, 2015.
13. J Lloyd-Price, H Tran, AS Ribeiro, Dynamics of small genetic circuits subject to stochastic partitioning in cell division, Journal of Theoretical Biology 356, 2014.
14. JG Chandraseelan*, SMD. Oliveira*, A Häkkinen, H Tran, I Potapov, A Sala, O Yli-Harja, M Kandhavelu, and AS Ribeiro, Effects of temperature on the dynamics of the LacI-TetR-CI Repressilator, Molecular BioSystems 9, 2013.
15. A Häkkinen, H Tran, B Ingalls, and AS Ribeiro, Effects of multimerization on the temporal variability of protein complex abundance. BMC Systems Biology 7, S3, 2013.
16. A Häkkinen, H Tran, O Yli-Harja, and AS Ribeiro Effects of rate-limiting steps in transcription initiation on genetic filter motifs, PLOS One, 8(8), 2013.