London - Jonathan Joseph has been dropped from the England side to face Italy in the Six Nations this weekend as the Bath centre was omitted from a 24-man squad announced by the reigning champions on Wednesday.
With Joseph out of contention for both a starting spot and even a bench position in the match day 23, England are set to field a new midfield combination against the Azzurri at Twickenham as they continue their quest for back-to-back Grand Slams.
Owen Farrell could move to flyhalf, with Elliot Daly - a try-scoring hero as a wing in England's 21-16 win over Wales last time out - and Ben Te'o the new centre duo.
Anthony Watson, fit following a hamstring injury, is in line for a place in England's back three, while up front James Haskell could start now that he is regarded as being fit enough for more than the 'finisher' role he has performed so effectively this Six Nations.
England coach Eddie Jones, speaking after the team's win over Wales in Cardiff earlier this month, made it clear he was contemplating changes for the Italy match.
"I've got some ideas of how we want to play against Italy, we will change it up a bit," said Jones, yet to lose a match as England coach.
"We want to play a different sort of game against them and it's a great chance for us to do something different," added the Australian, who became England boss after the team crashed out on home soil in the first round of the 2015 World Cup.
The former Australia and Japan coach has long made it clear his over-riding goal with England is to win the 2019 World Cup, something Jones believes will only be achieved if he increases the strength of the squad.
"Any changes will not be because I'm unhappy with the guys who played against Wales, but because I want to keep developing the team," said Jones after Daly's try with just four minutes left saw England to a dramatic come-from-behind win at Cardiff's Principality Stadium.
England, who've never lost to Italy, are on a 16-match winning streak.
They are just two shy of world champions New Zealand's all-time record of 18 successive Test victories by a leading or 'tier one' rugby union nation and will be firm favourites to closer to that mark against Italy, thrashed 63-10 by Ireland last time out.
Jones is due to name his side to face the Azzurri on Friday.
Forwards (13): Jack Clifford (Harlequins), Dan Cole (Leicester Tigers), Jamie George (Saracens), Dylan Hartley (Northampton Saints). James Haskell (Wasps), Nathan Hughes (Wasps), Maro Itoje (Saracens), Joe Launchbury (Wasps), Courtney Lawes (Northampton Saints), Joe Marler (Harlequins), Kyle Sinckler (Harlequins), Mako Vunipola (Saracens), Tom Wood (Northampton Saints)
Backs (11): Mike Brown (Harlequins), Danny Care (Harlequins), Elliot Daly (Wasps), Owen Farrell (Saracens), George Ford (Bath), Jonny May (Gloucester), Jack Nowell (Exeter Chiefs), Henry Slade (Exeter Chiefs), Ben Te’o (Worcester Warriors), Anthony Watson (Bath), Ben Youngs (Leicester Tigers)