A tool to track cell-to-cell contact

The Australian Synchrotron goes solar, and the Indian research satellite AstroSat detects ionising photons from a rare type of galaxy.

The new uLIPSTIC technology can track the physical interactions between cells, such as the above depiction of a dendritic cell activating a T cell. | Photo Credit: Rockefeller University

A fundamental goal of basic biology is understanding how diverse cell types work in concert to form tissues, organs, and organ systems. While recent efforts to catalogue the different cell types in every tissue in human bodies are a step in the right direction, they address only one piece of the puzzle. The big mystery of how those cells communicate with one another remains unaddressed and unsolved.

Since the advent of single-cell mRNA sequencing, researchers have been trying hard to connect the dots and explain how diverse cells unite to form tissue. The several existing methods of cataloguing cell-to-cell interactions have shortcomings. In the early efforts, involving direct observation under a microscope, interacting cells could not be retrieved for further analysis. With advanced imaging techniques used in subsequent developments, one could only infer how cells might interact on the basis of their structure and proximity to other cells. No approach captured the true physical interactions and signal exchange between cell membranes.

Now, a team of US scientists, led by Sandra Nakandakari-Higa of Rockefeller University, has designed a new tool called uLIPSTIC that lays the groundwork for a dynamic map that tracks the physical interactions between different cells and is capable of generating the set of all cell-to-cell interactions. uLIPSTIC is the culmination of work that began in 2018, which in principle can allow researchers to directly observe any cell-to-cell interaction in vivo. The work is described in a recent paper in Nature. “With uLIPSTIC we can ask how cells work together, how they communicate, and what messages they transfer,” said Rockefeller’s Gabriel D. Victora.

The new tool involves labelling cellular structures that touch when two cells make fleeting “kiss-and-run” contact before parting ways; if one cell “kissed” another, it would leave a mark much like lipstick, enabling easy identification and quantification of the cell-to-cell interaction.

The original platform that was designed had narrow applications, which recorded only specific kind of cell-to-cell interaction. The team decided to design a universal platform and came up with uLIPSTIC. In the original version of LIPSTIC, a “donor” cell used an enzyme borrowed from bacteria to place a labelled peptide tag onto the surface of an “acceptor” cell upon contact. “If you cram partner cells with enough enzyme and target, you can make any cell pair capable of LIPSTIC labelling without needing to know in advance what molecules these cells will use for their interaction,” said Victora.

Thus, uLIPSTIC does not require foreknowledge of molecules, ligands, or receptors. Scientists can now theoretically smear uLIPSTIC on any cell, without preconceived notions of how it will interact with its environment, and observe physical cell-to-cell interactions. The hope is that, eventually, uLIPSTIC will become a key tool to generate comprehensive atlases of cells interacting to form tissues.

Synchrotron on solar power

(Left) The main Australian Synchrotron building after solar panels were installed on its iconic circular roof. (Right) The building before it went solar. | Photo Credit:  ANSTO

THE Australian Synchrotron of the Australian Nuclear Science and Technology Organisation (ANSTO) is one of the country’s major research facilities and is located in Clayton, south-east Melbourne. A synchrotron is a kind of particle accelerator, a variant of the cyclotron in which the accelerating particle beam travels around a fixed closed-loop path, one of whose chief uses is as a powerful source of X-rays.

The rooftop of the main Australian Synchrotron building has been covered with more than 3,200 solar panels spanning a total area of 6,600 sq m. The installation was completed in five months. The 1,668 kWh solar panel system and inverter will supply part of the Australian Synchrotron’s total energy requirements. It is expected to save ANSTO more than 2 million kWh a year and reduce its carbon footprint by more than 1,680 tonnes of CO₂ a year. The envisaged monetary savings are about AUS$2 million (US$1.3 million) over the next five years. Michael James, the director of the facility, said: “The size of our rooftops, paired with the ample, uninterrupted exposure to sunlight at our location within the Monash precinct, was a major incentive for us to become more energy efficient.”

A galactic emission and the Big Bang

Images of the 10 LyC-leaking galaxies discovered, with the Astrosat UV deep field in the background. | Photo Credit: Inter-University Centre for Astronomy and Astrophysics, Pune

THE dedicated Indian multi-wavelength research satellite AstroSat, which was launched in September 2015, has detected ionising photons from a rare type of galaxy known as Lyman continuum (LyC) leakers. The discovery of 10 such galaxies, from the peak era of cosmic star formation history, makes it the first coherent sample of LyC leakers at this epoch.

The hydrogen atom is known to absorb photons only at wavelengths less than about 912 angstroms (Å, which is a 10th of a billionth of a metre), known as the Lyman limit, corresponding to a frequency of 3.29 million gigahertz and a photon energy of 13.6 electronvolts. The Lyman limit corresponds to the lowest energy photons absorbed by the hydrogen atom when an electron bound to a hydrogen nucleus can escape free. Photon energies above the Lyman limit lie entirely in the UV region of the electromagnetic spectrum, and thus the LyC photon energies lie in the extreme UV region. So, a detection of photons in this energy range by AstroSat was possible only with its on-board instrument UV Imaging Telescope (UVIT).

“Detecting ionising UV radiation from such galaxies is extremely challenging and was possible only because of the unique capabilities and high sensitivity of UVIT,” said Suraj Dhiwar, the lead author of this research work, which was recently published in The Astrophysical Journal Letters.

Within the first billion years of the Big Bang, the universe went through a major phase transition known as the reionisation phase, a process in which neutral hydrogen atoms dissociated into protons and electrons when they were struck by high energy UV photons in the LyC emission range. Understanding cosmic reionisation and the sources responsible for it remains one of the major unresolved problems in astronomy.

“The Lyman continuum emission can be easily absorbed or scattered by the interstellar medium or the circumgalactic medium of their host galaxies. Even when some of these ionising photons manage to come out of the galaxy’s environment, they may be absorbed by the vast intergalactic medium between us and the galaxy. This is what makes their discovery a rare event in astrophysics. Thanks to UVIT’s resolution and sensitivity that allowed us to create UV deep field in the far-ultraviolet filter,” said Kanak Saha, an associate professor at the Inter-University Centre for Astronomy and Astrophysics, Pune.

More interestingly, these LyC photons have wavelengths extending down to ~600 Å, falling in the extreme ultraviolet regime, the shortest UV wavelength with which a galaxy has been imaged so far. These galaxies are about 8−9 billion light years away from the earth and have intense star formation rates, with some of them forming massive young stars at a rate 100 times higher than the Milky Way galaxy. Beside the UV observation from Astrosat, the Hubble Space Telescope was used to obtain the optical/infrared imaging and spectroscopy for these rare galaxies.