Here, Press Association Sport examines five key talking points ahead of the Aviva Stadium clash.
Can Robbie Henshaw thrive at full-back?
British and Irish Lions centre Henshaw has been thrust into the 15 shirt for Saturday's match, reverting to the position where he first made his name. Henshaw made his Test debut at full-back in 2013, but has not played there for Ireland since. The 25-year-old has plenty of provincial experience in the role from his Connacht days, but has hardly operated at 15 for Leinster in the last few years. Head coach Joe Schmidt insists he boasts the "full spectrum of skills" to thrive this weekend, but only time will tell if he can cope with England's aerial bombardment.
Jack Nowell ready to go in new "libero" role
Exeter winger Nowell has revealed he has been given a "golden ticket" by coach Eddie Jones to roam in a free role against Ireland on Saturday. Jones previously half-joked he would deploy Nowell as an auxiliary flanker, a ninth forward, in Dublin. Quite how that manifests remains to be seen, but former Fiji Sevens coach Ben Ryan recently revealed on Twitter he utilised Isoa Damudamu as a 'libero' or sweeper in his days coaching Newbury. The tactic comes with far less flexibility than the football equivalent, but the idea remains the same – an all-court player operating in a free role in an ostensibly defensive remit, roaming around trying to steal ball wherever possible.
Bundee Aki and Manu Tuilagi lock horns for the first time since college
New Zealand-born Ireland centre Aki last faced England's Samoan midfielder Tuilagi in a college game some 12 years back. Aki donned Truro College colours to square up to Tuilagi's John Cleveland College, with the Leicester outfit apparently winning comfortably.
Back then a callow Aki insisted he steered clear of Leicester powerhouse Tuilagi – but this weekend there will be no quarter given by either party. Expect seismic collisions as two of the global game's most physical exponents hurtle straight down each other's channel.
Will Ireland bore England to death?
England assistant coach John Mitchell believes Ireland will bore England to tears this weekend. Ireland could not care less, but know full well there is nothing boring about winning a Grand Slam, or beating the much-vaunted All Blacks – as Joe Schmidt's men did in a stunning 2018.
Even a 3-0 home win would be viewed as scintillating by the Irish public. And when England are fully honest with themselves, they will admit that rather than boring, what they meant was that it is simply extremely difficult to pinch the ball off an Ireland team in full flow. Deny Ireland possession this weekend and England will have a chance. Should the hosts find their rhythm however, it could prove a long Dublin day for the visitors.
Mako and Billy could spell double trouble for Ireland
England finally have both Mako and Billy Vunipola fit, and Eddie Jones will love the chance to pair up the influential and physical brothers in his Red Rose pack. Billy Vunipola especially can transform England's game plan, especially in phase play, given his all-court skill-set. Ireland will have to shut down the Saracens number eight at source if they want to continue their winning Six Nations run.